synaptic plasticity

prenatal development

• pattern of connections emerges as a result of cell recognition events

• an axon guidance mechanism gets axons in approximately the right place

• there is a coarse retinotopic map, but the result is not nearly as good as normal retinotopy found in the adult → requires a second stage in development

postnatal development

• prenatal coarse pattern of connections refined by activity dependent mechanisms

• based on interactions between organism and its environment

• the influence on the environment on the brain changes with age

ocular dominance columns

• L/R segregated in layer 4C

• don’t see it in newborn cat

• above and below layer 4, binocular, but dominated by one eye or the other

• extend from pia to white matter

Hubel and Weisel OD column demonstration

• divided OD columns into 7 groups

• 1-7 contralateral → ipsilateral

experiment: sutured one eye shut at birth, raised monkey to 6 months, removed sutures and tested deprived animal’s visual responses

• V1 cells only driven by non-deprived eye

• monocular deprivation from birth-6 weeks in monkey, 12-13 weeks in cat → no binocular interactions

  • after this critical period, no effect of monocular deprivation

critical period in development

• time period in dvlpment when genetically determined patterns of brain circuitry are subject to environmental refinement

• cortex can change its wiring to appreciate the different input from the two eyes

imprinting

critical period is 2 days after hatching

ambliopia

• animals cortically blind in deprived eye

Comparing monocular, binocular, and alternating deprivation

Monocular: ambliopia

Binocular: normal distribution, but cells not quite normal → poor acuity

Alternating: OD bands sharper than normal, no binocular vision

alternating deprivation

• no binocular cells, no 3D depth perception

• strabismus (eye misalignment) gives same results → eventually lead to ambliopia

critical period for normal binocular vision development in humans

2-4 years

Child with strabismus

• initially has good vision (acuity), but cannot fuse image in 2 eyes because they favor one eye

• opthamologists used to delay correcting until 8/9, after critical period → children got amblopia

• mild strabismus: patch good eye for a few hours/day, strengthens eye muscles for alignment

• severe strabismus: surgical intervention to realign eyes

Formation of ocular dominance columns

• each projection initially spread out over full neural space of layer 4, trying to form their own topographical map of the retina

• In monocularly deprived eyes during critical period, deprived eye is at competitive disadvantage→ non-deprived eye continues to occupy cortical space they normally would have given up to the other eye

• competition for target space between fibers from the 2 eyes

• cooperation between fibers from the same eye

  • neural activity: critical factor regulating both competition and cooperation

Evidence of competition for target space between fibers from the 2 eyes

• monocular deprivation → competition reduced

• inputs from open eye form complete topographic map

• frog optic tectum: no competition → no columns

evidence for cooperation between fibers from the same eye

• retinal fibers spontaneously active in utero

• retinal neighboring cells tend to be active together, firing in synchronous bursts

• neighboring cells have similar patterns of activity (correlated activity) → LGN → cortex

• activity patterns in two eyes not correlated with each other

Strengthening/weakening synapses through cooperation/competition

• excited neurons synapses that are active together strengthened

• inactive/out of synchrony synapse fibers weakened

• results in precise retinotopic map and segregation of L/R eye influences in layer 4C

Hebb’s postulate for learning

• coincident activity in pre and postsynaptic elements of a synapse leads to its strengthening

• things that fire together, wire together

• strengthening of synapses in developing V1 is mediated by NMDA-receptor dependent mechanism

NMDA receptor

• glutamate receptor

• ligand and voltage gated ion channel (coincidence detector)

• at resting V_m, Mg²⁺ blocks channel

• depolarization → Mg²⁺ removed (+ ion repelled by positively charged inside)

• When nearby retinal ganglion cells fire at the same time → combined signals add up in the postsynaptic neuron

  • postsynaptic neuron’s V_m rises enough to kick out the Mg²⁺ block

  • NMDA receptors open → Ca²⁺ enters

    • activates signaling pathways inside the neuron → strengthens the synapses that were active

Effect of retinal lesions on cortical topography: plasticity in adult visual system

• Visual space is organized like a grid on the retina

• A small, targeted retinal lesion is made with a laser.

• When the visual cortex is mapped right after, the part that normally gets input from that damaged retinal spot becomes silent (a cortical scotoma).

• After about two months, mapping again shows that those previously silent neurons now respond, but to areas just outside the damaged region. Their receptive fields have shifted to the edges of the scotoma.

• As a result, the region of cortex representing the area around the lesion becomes enlarged, effectively “filling in” the missing visual space.

intrinsic horizontal synaptic connection

• V1 circuits that connect nearby columns with similar orientation tuning

• can be strengthened through cortical map modifications

Long-range horizontal connections

• Patchy, clustered similar connections linking distant orientation domains

perceptual learning

• requires plasticity in cortical connections

• task-specific