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Activity-dependent Development

Nature vs. Nurture

Development of ocular dominance in mammalian visual cortex

Critical period

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Roger Sperry David Hubel Torsten Wiesel

Nobel Prize in Physiology or Medicine 1981

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Regenerating retinal ganglion neurons project to their appropriate position

Axons know where to go; this process is NOT experience dependent. However, the details of the connection patterns between retina and tectum can be affected by experience (and electrical activity)

There is also some difference between regeneration (more specificity) and development (more “trial and error”)

Roger Sperry

normal frog frog with rotated eye

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Ocular dominance (OD) in mammalian visual cortex

layer 4

R L R L

R L R L

Rl Lr Rl Lr

Rl Lr Rl Lr

~ 0.5mm

left eye right eye left eye right eye

ocular dominance column

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Afferent pathways from the two eyes

right eye

left eye

LGN

left V1

nasal

temporal

6

5

43

21

CI

II

C

C Layer 4

left eyeright eye

R L

6

Categories of cells in terms of ocular dominance

od =

Response ipsi

Response ipsi + Response contra

od = 1, ipsilateral only

od = 0, contralateral only

od = 0~1, binocular

Eyes

Corticalcells

groups1 2 3 4 5 6 7

contra- equal ipsi-

Definition of ocular dominance index:

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OD distribution in normal adult V1 (monkey)

Normal adult V1 --

(above & below layer 4) binocular cells are common, with each eye well represented roughly equally

contralateral ipsilateralEqual

OD groups

Num

ber

of c

ells

Normal V1

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OD distribution in V1 after monocular deprivation

MD V1 --

Ocular dominance shifts to the non-deprived eye.

Animal blind in the sutured eye.

monocular deprivation (MD) -- suture one eye of the newborn animal (monkey) for several months, reopen.

Num

ber

of c

ells

V1 after monocularly depriving the contralateral eye

Equal

OD groups

contralateral ipsilateral

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Effect of monocular deprivation on OD was observed in multiple mammalian species

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Transneuronal dye to study the structure of OD columns

Areas which get inputs from the injected eye are labeled

left right radioactive

amino acid

2CI

II

C

C

layer 4

R L R LL

LGN

V1

eye

65

43

21

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Compare OD columns in newborns, adults and MD animals

normal adults - labeled and unlabeled alternate

new borns - no OD column, all areas are labeled

MD animals - deprived eye columns shrink, non-deprived eye columns expand

layer 4

layer 4

layer 4

deprived eye non-deprived eye

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Segregation of LGN afferents

- MD animals

1. axon terminals from the closed eye retract more

2. axon terminals from the open eye take over more areas

- normal adults

1. selective elimination of axon branches

2. local outgrowth of new axon branches

L R

layer 4

- new borns

1. single LGN afferent has lots of branches, covers a big area

2. axon terminals from the two eyes overlap extensively

L R

layer 4

layer 4

deprived eyeopen eye

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OD column formation is an activity-dependent, competitive process

Experiments:

1. Binocular injection of TTX, blocks segregation of OD columns

- segregation is activity dependent

2. If both eyes are deprived (binocular deprivation), OD columns are normal!

- segregation also depends NOT on the absolute level of activity, but on the balance between the input from the two eyes, thus seems to be competitive

Mechanism:

1. Normal development

- initially the axon terminals from the two eyes overlap

- at local region, inputs from one eye happen to be stronger

2. Monocular deprivation

- open eye more active, take over more territory

- deprived eye less active, lose most of the territory

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Critical period

1. Monocular deprivation (MD) causes a shift of OD toward the non-deprived eye. This is effective only before certain age. MD has no effect on adult animals.

critical period: a period in early life that the neural circuit is susceptible to external sensory inputs (e.g. MD). This period depends on the species and the neural circuit.

For OD in V1:

cat: 3rd week -- 3 months

monkey: first 6 months

human: 1st year most important, but extends to 5-10 years

2. MD within the critical period, the effect is permanent and irreversible.

This finding has profound implications in treatment of congenital cataracts in children

3. MD within the most sensitive part of the critical period (e.g., first 6 wk for monkey), a few day’s MD results in a complete loss of vision in the sutured eye.

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Critical periods of other neural functions

• visual system

- OD

cat: 3rd week ~ 3 months

monkey: first 6 months

human: 1st year, also extends to 5-10 year

- more complex visual functions (e.g., contour integration) often have longer critical period

• other aspects of brain function

- Bird imprinting behavior

Konrad Lorenz (1903-1989)

- Monkey social interaction

newborn monkeys reared in isolation for 6-12 months, behaviorally abnormal

- Human

- language: 2-7 years of age

- early social interaction:

withdrawn

nursing home babies

foundling homeno social interaction

normalwith social interaction