Plasticity In The Developing Nervous System

Question 1

Sensory inputs that may influence nervous development:

Answer 1

• visual = Ideal for study as easy to control degree of visual pathway stimulation during development
• olfactory (smell)
• tactile (feel)
• auditory

Question 2

Congenital cataracts:

Answer 2

= 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 months) had same effect: vision is permanently disrupted

Question 3

the mammalian visual system:

Answer 3

• 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) = filters out unimportant info
• Geniculate neurons innervate visual cortex for visual processing

Question 4

Hubel & Weisel:

Answer 4

• Studied cats/monkeys.
• When a kitten is born: it appears blind - After 10 days, first evidence of visual responses - Gradually, vision improves: animal develops ability to discriminate objects and patterns.
• if one eye is kept shut after birth = 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.

Question 5

Critical period:

Answer 5

= 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.

Question 6

why does suturing one eye shut during development cause permanent blindness?

Answer 6

= Blindness is associated with visual cortex

• experiments using microelectrodes on different parts of the visual pathway and shine light into eyes to ssee functional parts…
• Retinal ganglion neurons from open eye: normal light response.
• Cortical neurons from open eye: normal light response.
• Cortical neurons from closed eye: no light response.
• Therefore blindness associated with loss of activity from lateral geniculate nucleus (relay station) to visual cortex.

Question 7

What is happening to development of the visual cortex?

Answer 7

studied layer 4 of the visual cortex which receives ordered inputs from the lateral geniculate nucleus (relay station) in order to easily observe inputs from left and right eye via ocular dominance columns

Question 8

Layer 4 cells of the visual cortex -

Answer 8

process information about colour as well as processing spatial and orientation information

Question 9

Experimental labeling of ocular dominance columns:

Answer 9

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

• Inject radioactive proline (tagged with trtium, carbon or iodine-125) into single eye, which will be transported across synapses at the lateral geniculate nucleus and travels down axons to the visual cortex
• Remove brain and make serial sections of cortex.
• Conduct “autoradiography” on brain sections.
• Radiolabel detected on photographic film.
• Reveals axonal pathways derived from labelled eye = Light and dark stripes represent axon terminals originating from left and right eyes respectively.

Question 10

ocular dominance columns form during…

Answer 10

critical period

• Initially, after lateral geniculate nucleus neurons innervate layer 4 of the visual cortex, ODCs are not present: inputs from left and right eyes are intermingled.
• During critical period these inputs gradually segregate into ODCs.

Question 11

does sensory information change wiring of layer 4 of the visual cortex during the critical period?

Answer 11

Experiment:

• 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).

normal adult monkey = ODCs from both eyes take up equal territory.

18 mo. monkey, right eye closed during critical period = ODCs from open eye expand, whilst those of the closed eye become narrower.

Question 12

Hubel & Weisel’s conclusions:

Answer 12

= 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.

Question 13

How do environmental cues affect how nerve fibres occupy territory in the visual cortex?

Answer 13

envroinment - when one eye was removed from monkeys during development = found that the ocular dominance columns don’t form = both eyes needed for ODC formation.

• Blocking action potentials in both eyes has same effect: TTX (sodium channel blocker) injected into both eyes during critical period = no ODCs (electrical activity in both eyes is needed)

Question 14

Wiring of visual cortex is…

Answer 14

activity-dependent.

Question 15

The two eyes compete for…

Answer 15

territory in visual cortex.

- mediated by action potential firing

Question 16

normally…

Answer 16

both eyes receive same amount of light, fire to same degree: ODC size form to roughly equal size.

Question 17

Reduce activity in one eye…

Answer 17

ODCs from that eye shrink

Question 18

only have one eye…

Answer 18

no competition: no sorting of territory

Question 19

Amphibians don’t have ocular dominance columns…

Answer 19

• inputs from left an dright eyes project to opposite side of brain (no competition)
• 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.

Question 20

Roger Sperry -

Answer 20

Asked whether sensory information affected wiring of visual nerves.

• used adult newts as a model = useful as lesioned nerve processes regenerate

Question 21

amphibian visual system:

Answer 21

• no visual cortex, instead visual infor 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

= neurons in right eye only send info to left optic tectum and vice versa

Question 22

The amphibian visual map:

Answer 22

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.

Question 23

Why are retinotectal projections in amphibians inverted?

Answer 23

• To focus, light rays must be bent by the lens so that they have a point of convergence on the retina.

= 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.

Question 24

Sperry’s Question:

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

Answer 24

Sperry’s approach:

• Lesion retinotectal projections in newt.
• Disrupt orientation of retinal map.
• Let projections regrow.
• Test vision.

Question 25

Sperry’s experiment 1 -

Answer 25

Does vision recover normally if optic nerves cut?

• Cut adult optic nerves.
• Let nerves grow back to tectum.
• after recovery newt ate prey if it was infront or behind it = vision restored

= Post lesion, connections regenerate normally, innervating their correct targets in the tectum: retinotopic map restored

Question 26

Sperry’s experiment 2 -

Answer 26

What happens to nerve regeneration if information from retina is disorganised?

• Cut adult optic nerves.
• Rotate eyes 180°: invert receptive fields of retina = each point in space now represented by inverted cell type on retina (up side down/back to front)
• Let nerves grow back to tectum.
• after recovery, if prey is placed in front of newt it will think prey is behind it

= Retinal axons wire to their default locations: ignore information from eyes = Environmental information has no effect on wiring of visual system

Question 27

Sperry’s conclusions from experiment 2-

Answer 27

• 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.

Question 28

Consolidating Sperry’s and Hubel and Weisel’s results -

Answer 28

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

Question 29

can you fundamentally alter the function of discrete brain regions during the critical period? (rewiring the developing brain)…

Answer 29

• in newborn ferrets inputs from the eye can be wired to the auditory cortex

= cells of the auditory cortex now share many features with those of the visual cortex:

• Auditory cortex cells now respond to visual input.
• Auditory cortex cells form ocular dominance columns.
• Auditory cortex cells form an ordered retinotopic map.
• Auditory cortex cells display orientation, direction and velocity specific responses.
• ferrets can still distinguish between light and sound stimuli even though The only part of the brain to receive visual input is the auditory cortex

Question 30

Conclusion of topic…

Answer 30

Whilst genetic factors are fundamentally important to
nervous system development, experience also serves
critical functions.

Perturbing the activity of afferent inputs during the critical
period can dramatically alter brain development.

Therefore nature and nurture both have essential roles