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Edits to abstr, intro, fig3 legend in main.md

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2013-09-17 13:52:44 -04:00
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@@ -8,7 +8,7 @@ Mesoscale mapping of neural activity across developing cerebral hemispheres
# Abstract
The cerebral cortex exhibits spontaneous and sensory evoked patterns of activity during fetal and postnatal development that are crucial for the activity-dependent formation and refinement of circuits [#Katz:1996]. Knowing the source and flow of these activity patterns locally and globally is crucial to understanding self-organization in the developing brain. Here we show that neural population activity within newborn mice in vivo is characterized by spatially discrete domains that are coordinated in a state dependent and areal dependent fashion throughout developing isocortex. Whole brain optical recordings from neonatal mice expressing a genetic calcium reporter showed that ongoing activity in the cerebral cortex was characterized by discrete and repetitively active domains measuring hundreds of microns in diameter. Cortical domain activity depended on brain state with periods of localized and global domain synchrony exhibiting positive and negative correlations to motor behavior respectively. Furthermore, domain activity exhibited mirror-symmetric patterns between the hemispheres, with strong correlations between cortical areas that correspond to the default-mode network in primates. This study provides the first comprehensive description of population activity in the developing isocortex at a scope and scale that bridges the microscopic or macroscopic spatiotemporal resolutions provided by traditional neurophysiological or neuroimaging techniques. Mesoscale maps of cortical population dynamics within animal models will be vital to engineering future repair strategies and brain-machine interfaces for neurodevelopmental disorders.
The cerebral cortex exhibits spontaneous and sensory evoked patterns of activity during fetal and postnatal development that are crucial for the activity-dependent formation and refinement of circuits [#Katz:1996]. Knowing the source and flow of these activity patterns locally and globally is crucial to understanding self-organization in the developing brain. Here we show that neural population activity within newborn mice in vivo is characterized by spatially discrete domains that are coordinated in a state dependent and areal dependent fashion throughout developing isocortex. Whole brain optical recordings from neonatal mice expressing a genetic calcium reporter showed that ongoing activity in the cerebral cortex was characterized by distinct and repetitively active domains measuring hundreds of microns in diameter. Cortical domain activity depended on brain state with periods of localized and global domain synchrony exhibiting positive and negative correlations to motor behavior respectively. Furthermore, domain activity exhibited mirror-symmetric patterns between the hemispheres, with strong correlations between cortical areas that correspond to the default-mode network in primates. This study provides the first comprehensive description of population activity in the developing isocortex at a scope and scale that bridges the microscopic or macroscopic spatiotemporal resolutions provided by traditional neurophysiological or neuroimaging techniques. Mesoscale maps of cortical population dynamics within animal models will be vital to engineering future repair strategies and brain-machine interfaces for neurodevelopmental disorders.
@@ -17,7 +17,7 @@ The cerebral cortex exhibits spontaneous and sensory evoked patterns of activity
<!--- This should be one paragraph. Some of this intro material could be combined with intro or concl sentences in abstract for a Nature letter (should be referenced and up to 300 words; 200 words preferred) --->
Brain development requires neural activity and calcium dynamics for establishing proper circuit structure and function. The importance of neural activity in the prenatal and neonatal period can be easily recognized in children exposed to chemical agents affecting neurotransmission during the fetal period that result in severe brain malformations, epilepsy, and mental retardation. Indeed, embryonic limb movements in species ranging from chick to human are thought to be initiated by spontaneous motor neuron activity in the spinal cord and has been recognized in chick to human and is thought to be crucial for activity-dependent development of motor synapses [Schoenberg:2003] [Marder,Lichtmann]. However it is only recently that we have begun to appreciate the underlying patterns of persistent neural activity that in fact exist in the developing brain in vivo. For example, sensori-motor feedback associated with spontaneous movement generated by spinal motor neurons triggers synchronized 'spindle-burst' potentials among cells in somatosensory cortex [Yang:2009][Khazipov:2004a] before the start of locomotion and tactile behavior. Correlated bursts of activity occur in the developing rat hippocampus in vivo [#Leinekugel:2002] [Mohns&Blumberg]. Spontaneous retinal waves drive patterned activation of circuits throughout immature visual system before the onset of vision [#Ackman:2012] [Hanganu,Colonnese?]. Furthermore, prenatal EEG recordings have demonstrated spindle burst oscillations and slow activity transients in the human infant somatosensory and occipital cortices before birth [#Vanhatalo:2005][#Tolonen:2007]. However, a comprehensive account of the structural dynamics of persistent activity throughout the developing isocortex in vivo has not been undertaken.
Brain development requires neural activity and calcium dynamics for establishing proper circuit structure and function. The importance of neural activity in the prenatal and neonatal period can be easily recognized in children exposed to chemical agents affecting neurotransmission during the fetal period that result in severe brain malformations, epilepsy, and mental retardation. Indeed, embryonic limb movements in species ranging from chick to human are thought to be initiated by spontaneous motor neuron activity in the spinal cord and is thought to be crucial for activity-dependent development of motor synapses [Schoenberg:2003] [Marder,Lichtmann]. However it is only recently that we have begun to appreciate the underlying patterns of persistent neural activity that in fact exist in the developing brain in vivo. For example, sensori-motor feedback associated with spontaneous movement generated by spinal motor neurons triggers synchronized 'spindle-burst' potentials among cells in somatosensory cortex [Yang:2009][Khazipov:2004a] before the start of locomotion and tactile behavior. Correlated bursts of activity occur in the developing rat hippocampus in vivo [#Leinekugel:2002] [Mohns&Blumberg]. Spontaneous retinal waves drive patterned activation of circuits throughout immature visual system before the onset of vision [#Ackman:2012] [Hanganu,Colonnese?]. Furthermore, prenatal EEG recordings have demonstrated spindle burst oscillations and slow activity transients in the human infant somatosensory and occipital cortices before birth [#Vanhatalo:2005][#Tolonen:2007]. However, a comprehensive account of the structural dynamics of persistent activity throughout the developing isocortex in vivo has not been undertaken.
- Neural activity, drugs, and birth defects
@@ -37,7 +37,7 @@ Brain development requires neural activity and calcium dynamics for establishing
# Results
## Ongoing activity in the developing cerebral cortex is characterized by discrete domains
## Ongoing activity in developing isocortex is characterized by discrete domains
* Cortical column (mini/meso/super columns) history (20th century anatomists-- sherrington, valverde, rakic, etc).
* Column physiology-- Hubel and Wiesel. Rodent V1?
@@ -53,7 +53,7 @@ Brain development requires neural activity and calcium dynamics for establishing
metric | mean | min | max | unit
------------- | ----- | ---- | ------ | --------------------
diameter | 396.0 | 22.7 | 2383.5 | µm
diameter | 396.0 | 22.7 | 2383.5 | µm
duration | 0.6 | 0.2 | 14.6 | s
frequency | 2.9 | | | domains/sec/hemisphere
[**Table 1: Domain statistics**]
@@ -111,15 +111,7 @@ lenActvFraction>0 | fracCorr | timeCorr_s | fracCorrPos | timeCorrPos_s | fracCo
<!--- * Each hemisphere 'training' the other one in preparation for behaviorally relevant sensory-motor imitations '[[mirror_neurons]]' hypothesis? --->
![**Figure 3.** Cortical domain activity exhibits bilateral symmetry. **a** Examples of domains exhibiting spatially symmetric activations. Notice most timepoints contain a mixture of symmetric and asymmetric domain activations. **b** Hemispheric domain centers of mass for coactive frames in a recording along medial-lateral (ML) and anterior-posterior (AP) extents. Bottom panels show the periods indicated by black bars at expanded view. **c** Plot of hemispheric domain centers of mass for coactive frames. **d** Correlation matrix of domain activity among cortical areas.](figure3.png)
xy pearson corr coef ML | xy pearson corr coef AP
--- | ---
p = 1.1591e-28 | p = 7.0982e-07
*scatterplots in figure 3* ||
![**Figure 3.** Cortical domain activity exhibits bilateral symmetry. **a** Examples of domains exhibiting spatially symmetric activations. Notice most timepoints contain a mixture of symmetric and asymmetric domain activations. **b** Hemispheric domain centers of mass for coactive frames in a recording along medial-lateral (ML) and anterior-posterior (AP) extents. Bottom left panels show the periods indicated by black bars at expanded view. Pearson's correlation: ML, p = 1.1591e-28; AP, p = 7.0982e-07. **c** Correlation matrix of domain activity among cortical areas.](figure3.png)
@@ -130,6 +122,8 @@ p = 1.1591e-28 | p = 7.0982e-07
<!--- # References --->
<<[references.txt]
<!--- # Metadata --->
<!---Figure 1 metadata
* neonate_ms_fig.png
* binary masks: Screen_Shot_2013-03-29_at_12.06.25_PM_crop.png, ..._crop1.png, ..._crop2.png