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Flashcards in McDearmid Deck (41)
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Describe congenital cataracts

Cataract: clouding of the lens

If removed in later life (10-20 yrs of age): permanently disrupted vision.

If removed in infancy: vision not impaired.

Raising monkeys in darkness (for first 3-5 mo.) had same effect.


Describe David H. Hubel & Torsten N. Weisel's experiment

- Hubel and Weisel shared the 1981 Nobel Prize in Physiology/
Medicine with Sperry for describing plasticity in the developing visual system.

- Studied cats/monkeys.

- When a kitten is born: it appears blind.

- After ca. 10 days, first evidence of visual responses.

- Gradually, vision improves: animal develops ability to discriminate objects and patterns.

- Result: Permanent blindness in closed eye when later opened.

- Only occurs if vision disrupted during ‘critical period ’ in development (first 12 weeks after birth in cat).

-Does not occur if you do same experiment in adult.


Describe the mammalian visual system

- Forward-looking mammals have binocular vision: both eyes work together to generate a composite image.

- Each side of the brain receives inputs from both eyes

- Fibers from retina innervate lateral geniculate nucleus (relay station).

- Geniculate neurons innervate visual cortex.


Describe the critical period

- A time during development when an organism is more susceptible to environmental influences than at later stages.

- During critical periods in nervous development, brain maturation can be influenced by changes in environmental conditions

- Lorenz - imprinting birds 12-17h after hatching


Which part of the brain was used for the study of visual cortex development

- Blindness associated with loss of activity from LGN to visual cortex.

- Hubel and Weisel needed a structure in visual cortex where inputs from left and right eyes are easy to observe.

- One part the visual cortex receives ordered inputs from LGN. This region is called “layer 4”

- Projections from the LGN innervate this structure in “eye specific columns” (in other regions inputs not organised this way)

- Thus, layer 4 can be used to study amount of cortical territory that is innervated by each eye


What are ocular dominance columns? (ODC)

- “the tendency of groups of nerve cells in layer 4 of visual cortex to preferentially receive inputs from one eye or the other”.


Describe experimental labelling of ODCs

Transneuronal labelling: allow tracing of afferent projections originating from each eye.

“Retrograde neuronal tracing”
- Inject radioactive proline into single eye (tagged with 125I, tritium or carbon).
- Proline transported towards nerve terminal of RGCs
~ Crosses synapses (“transynaptic labelling”) at LGN
~Travels down LGN axons to visual cortex.
- Remove brain. Make serial sections of cortex.
- Conduct “autoradiography” on brain sections.
~ Radiolabel detected on photographic film.
~ Reveals axonal pathways derived from labelled eye.


What do ODC look like

- Light and dark stripes represent axon terminals originating from left and right eyes respectively.
- Looks like patterns in the sand under the sea/sand dunes


When do ODC form?

- Emerge gradually during the critical period
- Initially, after LGN neurons innervate C4, ODCs are not present: inputs from left and right eyes are intermingled.
- During critical period these inputs gradually segregate into ODCs.


Does sensory information change wiring of C4 during the critical period?


Suture one eye in cat/monkey during critical period.

Subsequently open eye.

Transneuronal labelling to label layer 4 territory occupied by each eye.

Compare to control animals (both eyes open during development).


What difference does the closed eye make

Instead of ODC taking up equal territory the ODC from the open eye expands whilst those of the closed eye become narrower


Describe Hubel and Wiesel's conclusions

- Permanent loss of brain responses to visually deprived eye are due to permanent loss of inputs from that eye to visual cortex.

- During critical period of development, wiring of the visual system can be permanently altered by experience.


Describe Pasko Rakik

- Monkey experiments:
Surgically remove one eye during development
- Examine ODCs in layer 4 at 2 months post birth
- Inputs from remaining eye do not sort into columns.
- Similar results obtained if both eyes sutured shut (Swindale, 1981).
- So: both eyes needed for ODC formation.


Describe Stryker and Harris

- 1986
- Blocking action potentials in both eyes has same effect:
- TTX (sodium channel blocker) injected into both eyes during critical period: no ODCs!!!!!!


How do environmental cues ‘instruct’ nerve fibers to occupy territory in the visual cortex?

- But, if you reduce action potential firing in one eye (via TTX injection)
- You get expansion in size of ODCs from untreated eye at expense of TTX-injected eye (Chapman et. Al. Nature 1986. 324. pp 154-156)
- Similar to suture experiments
- So changing the balance in firing activity in neurons associated with the left and right eyes affects ODC formation.


How do environmental cues ‘instruct’ nerve fibers to occupy territory in C4?

- Wiring of visual cortex is activity-dependent.
- The two eyes compete for territory in visual cortex.
- Competition mediated by action potential firing.
- Normally both eyes receive same amount of light, fire to same degree: ODC size form to roughly equal size.
- Reduce activity in one eye: ODCs from that eye shrink.
- Abolish competition: no sorting of territory.


Describe activity dependence

- Active neurons induce activity-dependent release of trophic factors (eg. neurotrophins) from postsynaptic cell.
- "Neurons that fire together wire together”
- Neurons are successful if they fire synchronously to strongly activate postsynaptic cell.


How are amphibians different

- They don't have ocular dominance
- Since ganglion cells from each eye only project to their respective contralateral parts of the brain, nerve fibers from the eyes do not compete for territory in the tectum.


Describe weird frog experiment

- Constantine-Patton and Law (1978) Science 202: 609-641
- Transplant a third eye onto frog (Rana pipiens). Let axons wire up to tectum.
- This suggests that all you need for segragation of territory to occur is afferent input from two different pathways converging on same target
- Activity-dependant


Who is Roger Wolcott Sperry

- 1981: Nobel Prize in Physiology/Medicine
(for describing distinct roles of left and right brain
- Corpus callosotomy: treatment for epilepsy (in 1940-50’s).
- Involves surgically cutting the corpus callosum, the nerve tracts that connect the two halves of the cortex.
- Sperry studied “split brain- patients”
- Found the left and right hemispheres have different specialisations
- Left hemisphere: dominance for language
- Right hemisphere: dominance for visual spatial processing


Why did Sperry use adult newts

-At the time of Sperry’s experiments it was difficult to perform studies on developing animals (small size).
- Adult amphibians: useful as lesioned nerve processes regenerate.


How is amphibian visual system organised

- 'Lower vertebrates'
- Visual information processed by optic tectum
- Newts have monocular vision: eyes work separately, forming two different images
- Entire visual field for each eye sent to the contralateral optic tectum.


Describe the amphibian visual map

(1) Each point in space is represented by a separate location on the retina.
(2) Ganglion cells connect map each point on retina to a specific point on the tectum: forms retinotopic map of visual space.
- Anterior ganglion cells: map to posterior optic tectum.
- Posterior ganglion cells: map to anterior optic tectum
- Dorsal ganglion cells: map to ventral optic tectum.
- Ventral ganglion cells: map to dorsal optic tectum


Why are retinotectal projections inverted

- To focus, light rays must be bent by the lens so that they have a point of convergence on the retina.
- In doing so, the image becomes inverted (upside down, back-to-front) on the retina.
- Retinotectal projections wire into the tectum in an inverse orientation: image is reverted to the correct orientation when processed by the brain.


What was Sperry's Q?

Can the environment influence the way in which ganglion cells map onto tectal cells?


How did Sperry approach his Q?

Lesion retinotectal projections in newt.

Disrupt orientation of retinal map.

Let projections regrow.

Test vision.


Describe experiment 1: control

- Does vision recover normally if optic nerves cut?
- Cut adult optic nerves.
- Let nerves grow back to tectum.
- Prey placed in front and behind successfully captured
- Conclusion: normal vision restored
- Post lesion, connections regenerate normally, innervating their correct targets in the tectum:retinotopic map restored


Describe experiment 2: What happens to nerve regeneration if information from retina is disorganised?

- Cut adult optic nerves.
- Rotate eyes 180°: invert receptive fields of retina.
- Let nerves grow back to tectum.
- Rotated eye: each point in space now represented by inverted cell type on retina
- Newts ran away from flies
- Retinal axons wire to their default locations: ignore information from eyes
- Environmental information has no effect on wiring of visual system


What did Sperry conclude

- Newts always responded this way: they could not learn to make correct responses.
- Sperry hypothesized: Connections form innately and cannot be reconfigured.
- Sperry correct: nerve regrowth depends on gradients of axon guidance molecules (ephrins) that are genetically determined.


Consolidating Sperry’s and Hubel and Weisel’s results

- Axon guidance not influenced by environmental inputs (Sperry): Axon guidance cues are genetically determined
- Refinement of synaptic connections is influenced by environmental inputs (Hubel/Weisel): activity dependent stabilization of synapses