class 13: activity dependent refinement of sensory maps

coarse molecular targeting of sensory map

utilize genetic gradients and molecular labels to guide growing retinal axons to initial correct target regions

• molecular cues alone lack resolution to specify every individual axon branch and synapse

activity-dependent refinement of sensory map

supplies relational information by evaluating patterned neural firing (especially which neurons fire together & with what timing) to stabilize, weaken, or eliminate initially overlapping connections at fine spatial & functional scales

what are ocular-dominance columns

striped arrangements of layer IV of primary visual cortex that group neurons according to relative functional influence or preference they receive from either left or right eye

how does early monocular deprivation alter ocular-dominance physiology & anatomy

• physiological: dramatic shift in cortical responsiveness toward open (non-deprived) eye. neurons that normally respond to binocular input lose drive from deprived eye, while neurons receiving deprived eye inputs become silent or weakly driven.

• anatomy: geniculocortical axon terminals transmitting input from deprived eye undergo physical shrinkage and arbor retraction within layer IV of V1, forfeiting cortical territory to terminals from open eye

why do monocular deprivation and binocular deprivation produce different ocular-dominance outcomes?

difference lies in relative competitive balance:

• monocular: creates severe activity imbalance between eyes. strongly active open eye acts as consistent winner in Hebbian competition, outcompeting and driving structural shrinkage of weak inputs from deprived eye.

• binocular: reduces total visually driven activity equally across both eyes. because neither eye possesses competitive advantage, competition cannot occur and ocular dominance remains balanced acros V1

what does strabismus reveal about role of correlated binocular activity?

it causes both eyes to be active, but because they view different parts of scene, inputs arrive at visual cortex asynchronously.

• temporary correlated binocular activity is required for integration, causing loss of binocularly driven cortical neurons.

what is a critical period?

a restricted developmental window during early life when neural circuits exhibit heightened plasticity and responsiveness to sensory experience

why does timing of deprivation or treatment matter for amblyopia?

• during critical period, abnormal visual inputs (monocular deprivation) rapidly alters cortical wiring through active competition. reopening eye during this period allows for robust recovery.

• as critical period close, cortical plasticity declines.

• if treatment occurs after critical period ends, structural & functional visual deficits become resistant to recovery → leading to permanent amblyopia

why can retinal waves (but not patterned visual experience) guide earliest eye-specific segregation in LGN?

eye-specific projections in lateral geniculate nucleus segregate prenatally, prior to maturation of photoreceptors and bipolar cells rewuired to transduce light & convey visual scenes

• because photoreceptors are non-functional at this early stage, patterned. visual experience cannot guide this process. instead immature retina spontaneously generates self-organized AP that propagate across retinal ganglion cells.

stage 1 retinal waves (prenatal)

gap junction coupling among ganglion cells & immature amacrine cell networks

• spatiotemporal pattern: slow, sparse correlations

• developmental functions: establishes coarse retinotopic alignment in SC and LGN

stage 2 retinal waves (perinatal to neonatal)

acetylcholine released by amacrine cells acting on nicotinic ACh receptors on RGCs

• spatiotemporal pattern: local propagating bursts, coactive within an eye, independent between eyes

• developmental functions: drives eye-specific layer segregation in LGN & SC and refines intra-eye retinotopy

stage 3 retinal waves (postnatal)

glutamate release from functional bipolar cells acting on AMPA & NMDA receptors

• spatiotemporal pattern: faster, temporally precise waves

• developmental functions: refines retinotopic precision, strengthens selected synapses, prepares circuits for eye opening

how does the correlation structure of stage 2 waves support cooperation within an eye

operates via Hebbian synaptic mechanism

• because neighboring inputs from same eye fire coactively, their combined presynaptic signals repeatedly depolarize shared postsynaptic target neurons, reinforcing & stabilizing each others connection

how does correlation structure of stage 2 waves support competition between eyes

operates via hebbian synaptic mechanism

• because waves generated by opposite eyes are uncorrelated, inputs from two eyes arrive at postsynaptic targets at different times.

• when one eye’s input depolarizes target neuron, asynchronous inputs from opposite eye fail to participate, causing un-correlated terminals to weaken and segregate into separate ocular territories

what did three-eyed frog experiment show?

grafting third eye onto a tadpole forces two distinct retinal axon populations to innervate single optic tectum (which normally receives input from only one eye). competing axon terminals spontaneously segregate into alternating eye-specific stripes

• proved that eye-specific sorting does not require pre-programmed target map, but emerges naturally when coactive inputs cooperate and asynchronous ensembles compete

three-eyed frog experiment → what additional conclusion came from applying NMDA receptor antagonist?

caused eye-specific stripes to reversibly desegregate and blur

• postsynaptic NMDA receptors act as necessary coincidence detectors → directly coupling correlated synaptic activity to physical axon sorting

what does rewired-ferret experiment demonstrate about relative roles of afferent input

patterned sensory input plays instructive rule in constructing complex functional cortical architecture (such as orientation maps)

• operates within tissue-intrinsic limits

what does rewired-ferret experiment demonstrate about relative roles of intrinsic cortical programs

intrinsic genetic expression profiles, laminar organization, and local cortical circuit rules constrain what features tissue can ultimately construct

rewired-ferret experiment

visual retinal projections were surgically redirected through auditory thalamus (MGN) into primary auditory cortex (A1). rewired auditory cortex developed organized visual orientation-selective modules

how does an MNDA receptor detect coincident presynaptic activity

glutamate release from presynaptic terminal, which binds to receptor

how does an MNDA receptor detect coincident postsynaptic activity

significant postsynaptic membrane depolarization (driven by coactive AMPA receptors), which expels Mg blocking the pore at resting membrane potential

three consequences of resulting calcium signal

• short-term synaptic efficacy & receptor trafficking (alters AMPA trafficking & synaptic strength)

• transcriptional changes (activates Ras-ERK to alter gene expression)

• structural plasticity (regulates local cytoskeletal machinery to stabilize dendritic spines)

what is homeostatic scaling?

negative-feedback mechanism that globally adjusts overall synaptic gain to keep average firing rates

• uniformly increasing or decreasing AMPA receptors across all synapses of cell

how does homeostatic scaling complement hebbian synaptic competition?

stabilizes overall network activity w/o destroying relative differences in individual synaptic weights established by hebbian

hebbian synaptic competition

operates locally & selectively to strengthen coactive correlated synapses and weaken uncorrelated ones

• unconstrained hebbian positive feedback can cause network instability (complete synaptic silence)