Let’s begin by going discussing one of the fantastic true stories told by the famous NYC neurologist, Oliver Sacks, who passed away just a few months ago and who weaved engaging clinical accounts and wrote a number of best selling books regarding cases of patients having extraordinary behaviors that resulted from strange or unknown neurological disorders including this one called The Man Who Mistook his Wife for a Hat. —>Indeed one of these accounts was about a man who actually mistook his wife’s face for a hat. This man, who was an accomplished musician and teacher at a school of music had developed trouble seeing faces and recognizing many types of objects in general as a result of degeneration in the visual system, likely from a stroke or something.
…these types of stories summarize a large bit of what neuroscience is about— understanding fundamental circuits that comprise brain function and animal behavior as well as the dually fascinating and devastating consequences that occur when the formation of those fundamental circuits goes awry.
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## Brain damage and visual perception
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* The patient (‘Dr. P’):
* good visual acuity & color vision
* good recognition of abstract geometric objects (cubes, spheres, etc)
* Trouble recognizing friends, family, pupils
* Trouble recognizing complex objects
* Describing a rose: “About six inches in length. A convoluted red form with a linear green attachment”
* Describing a glove: “A continuous surface, infolded on itself. It appears to have five outpouchings”
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Let’s begin by going discussing one of the fantastic true stories told by the famous NYC neurologist, Oliver Sacks, who passed away just last summer and who weaved engaging clinical accounts and wrote a number of best selling books regarding cases of patients having extraordinary behaviors that resulted from strange or unknown neurological disorders including this one called The Man Who Mistook his Wife for a Hat. —>Indeed one of these accounts was about a man who actually mistook his wife’s face for a hat. This man, who was a well regarded and accomplished musician and teacher at a NY school of music had developed trouble seeing faces and recognizing many types of objects in general as a result of degeneration in the visual system, likely from a stroke.
This patient (let’s call him Dr. P)… was cognitively sharp, had good vis…
Hard time...
visual agnosia, prospognosia, lesion somewhere in temporal lobe of the cerebral cortex for reasons we will hopefully discover partially by the end of today’s class.
For him the visual world was a series of lifeless abstractions, seeing and describing the world almost the way a machine would see it without grasping the big picture.
…these types of stories summarize a large bit of what neuroscience is about— understanding fundamental circuits that comprise brain function and animal behavior as well as the dually fascinating and devastating consequences that occur when the formation of those fundamental circuits goes awry.
Neighboring retinal ganglion cells in the eye detect changes in contrast from similar portions of the visual field, thus forming a 2D map of visual space in the retina. This spatial representation of objects in the retina is then projected onto -->multiple down stream visual areas, so that maps of retinal topography, or retinotopy, are maintained at multiple levels in the visual system.
Other visual functional organization that is present at birth includes maps of ocular dominance, where the responses of neuronal groups is dominated by that of one eye or the other and orientation selectivity where the responses of neighboring neurons is dominated by high contrast edges of particular orientation.
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## Intrinsically photosensitive RGCs (containing melanopsin) are required for day/night activity cycles
* At the optic chiasm, visual information from the two sides of the head cross
* In animals with eyes on the sides of the head, the entire visual field for each side is sent to the opposite side of the brain (to the tectum)
* In forward-looking animals, the visual image is split
* An object on the right side of the visual field is seen by both left hemi-retinae (but not by the right hemi-retinae). The optic nerves leave the retinae, and at the optic chiasm, the two left hemi-retinae projections go left, while the two right hemi-retinae go right
The organization of connections from each eye is shown here where if we were to look at a chunk of primary visual cortex from ferrets, cats, or monkeys we would find ocular dominance columns where the response properties of neighboring cells is dominated by that of one eye or the other and which can be demonstrated by electrophysiological recordings or by histological staining for cytochrome oxidase.
Overlaid on this map of alternating ocular dominance columns is a map of orientation pinwheels in visual cortex shown by the isocontour lines on the surface *here* and by the colored orientation map *here* -->where the colored map represents the preferred response of neighboring neurons to high contrast edges presented at different orientations in the visual field.
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## Columnar organization of ocular dominance
<div><img src="figs/PN12132_f1003e0.jpg" height="100px"><figcaption>Neuroscience 2e Sinauer 2001</figcaption></div>
<div><img src="figs/PN12131_f44cd94.jpg" height="100px"><figcaption>Neuroscience 2e Sinauer 2001</figcaption></div>
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## Localization of multiple visual areas in the human brain using fMRI
<figure><img src="figs/Neuroscience5e-Fig-12.17-1R_copy_1a1c7c2.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 12.17</figcaption></figure>
<figure><img src="figs/Neuroscience5e-Fig-12.17-2R_copy_7168914.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 12.17</figcaption></figure>
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## Subdivisions of the extrastriate cortex in the macaque monkey
but he also emphasized that “the brain is a complex of widely and reciprocally interconnected systems and that the dynamic interplay of neural activity within and between systems is the very essence of brain function”. And indeed if you look at this—> anatomical wiring diagram for different visual areas represented by different colors you will notice that we use an organized constellation of brain regions to process and route different types of visual information and each one of these brain regions consists of many thousands of these basic cortical column building blocks described on the previous slide.
Invariant visual representation by single neurons in the human brain. Quiroga et al., Nature 2005
Recordings were made in medial temporal lobe of the cerebral cortex including entorhinal cortex and hippocampus course of clinical procedures to treat epilepsy.
Interestingly this cell did not respond to pictures of Jennifer Aniston with Brad Pitt, maybe this cell had ‘moved on’ just like Miss Aniston. But other cells in this work did respond to selectively to Aniston with her friend’s costar Lisa Kudrow.
One object per neuron?
however these results may be best understood in a non-visual context. Some of the example cells responded not only to pictures but also to the printed name of a particular person or object. So this type of invariance must be based off learned associations.
invariant visual representation by single neurons in the human brain. Quiroga et al., Nature 2005
Connor Nature 2005, N&V on Quiroga et al:
>a more technical term for the grandmother issue is ‘sparseness’.
>At earlier stages in the object recognition pathway the neural code for an object is a broad activity pattern distributed across a population of neurons, each responsive to a discrete visual feature. At later, higher order processing stages, neurons become increasingly responsive for combinations of features and the code becomes increasingly sparse.
## Short-term plasticity of the gill-withdrawal reflex in sea slugs
Facilitation in the marine mollusk *Aplysia californica*
<div><img src="figs/Neuroscience5e-Fig-08.03-1R_copy_3f9f1c7.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.3</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-08.03-2R_copy_2b59a30.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.3, Squire and Kandel 1999</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-08.03-3R_copy_0fbd016.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.3, Squire and Kandel 1999</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-08.03-4R_copy_784bb55.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.3, Squire and Kandel 1999</figcaption></div>
Note:
Squire and Kandel. *Memory: From Mind to Molecules* 1999
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## Epilepsy
Disorder characterized by periodic seizures from synchronous firing of large groups of neurons in the nervous system. Kindling and synaptic plasticity plays a role.
<figure><img src="figs/Neuroscience5e-Box-08C-0_57467fe.jpg" height="100px"><figcaption>Neuroscience 5e Box 8C, Dyro 1989</figcaption></figure>
Reid et al., Prog Neurobiol 2009
Scheffer adn Berkovic Trends Pharm Sci 2003
McNamara et al., STKE 2006
Engel 2008, *Epilepsy: A Comprehensive Textbook*
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## Synaptic mechanisms of short-term sensitization in sea slugs
<div><img src="figs/Neuroscience5e-Fig-08.04-1R_copy_840c43d.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.4</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-08.04-2R_copy_7c288a4.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.4, Squire and Kandel 1999</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-08.04-3R_copy_9e8b3eb.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.4, Squire and Kandel 1999</figcaption></div>
Note:
Squire and Kandel. *Memory: From Mind to Molecules* 1999
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## Molecular signals underlying short- and long-term sensitization in *Aplysia*
<div><img src="figs/Neuroscience5e-Fig-08.05-1R_copy_1739967.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.5, Squire and Kandel 1999</figcaption></div>
unindentified proteins responsible for synaptic growth (yellow)
</figcaption><img src="figs/Neuroscience5e-Fig-08.05-2R_copy_2b6b868.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.5, Squire and Kandel 1999</figcaption></div>
Note:
Squire and Kandel. *Memory: From Mind to Molecules* 1999
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## CamKII signaling in a dendritic spine during LTP
<div><img src="figs/Neuroscience5e-Fig-08.11-1R_d67561b.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.11</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-08.11-2R_f40021e.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 8.11, Lee et al., *Nature* 2009</figcaption></div>
* Onset during adolescence– hallucinations, delusions, and paranoia. Positive symptoms
* Social withdrawal, lack of motivation, cognitive impairment- Negative symptoms
* Chlorpromazine and reserpine are drugs that alleviate positive symptoms, with side effects
* Reserpine interferes with metabolism of all three monoamine neurotransmitters– dopamine, norepinephrine and serotonin by inhibiting a vesicular monoamine transporter (VMAT) effectively depletes the levels of these neurotransmitters
