Chronic monocular deprivation, initiated early in postnatal life and

maintained until adulthood, causes severe amblyopia, characterized by a

significant decrease in strength and selectivity of visual cortical responses

evoked by stimulation of the deprived eye. Amblyopia is highly resistant to

reversal in adulthood, but binocular visual deprivation through dark exposure can

be used to promote recovery from chronic monocular deprivation. To identify the

locus of the changes in excitatory synaptic transmission that accompany the

response to, and recovery from chronic monocular deprivation, I quantified the

density of dendritic spines throughout the depth of the primary visual cortex. I

demonstrate that chronic monocular deprivation induces a significant loss of

dendritic spine density in all cortical laminae. Importantly, recovery of visual

responses induced by dark exposure followed by reverse deprivation is

accompanied by a significant recovery of dendritic spine density. As the majority

of excitatory synaptic transmission is mediated by spine synapses, this suggests

significant loss and recovery of excitatory synaptic density during loss and

recovery of vision. The observation that mid cortical laminae, which are enriched

for thalamocortical synapses, participates in the recovery from chronic monocular

deprivation in adulthood was unexpected, given that plasticity at thalamorecipient

synapses has been demonstrated to be constrained very early in

postnatal life. Isolation of the thalamocortical component of the visually evoked

potential via cortical silencing confirmed an experience-dependent strengthening

during the recovery from amblyopia. This work further supports the hypothesis

that dark exposure in adulthood returns the visual cortex to a "juvenile" state,

capable of expressing plasticity at thalamocortical synapses.

Severe amblyopia is characterized by a loss of the strength and selectivity

of visually evoked activity in primary visual cortex. The reduction in visually

evoked responses recovers completely when dark exposure is followed by

reverse deprivation (open deprived eye, close nondeprived eye). However, the

recovery of spatial acuity, measured by performance in a spatial frequency

discrimination task, is incomplete. Therefore, I designed a strategy to promote

the strengthening of synapses serving the deprived eye that utilizes tetanic visual

stimulation. Dark exposure followed by visual tetanus induced a significant

strengthening of synapses serving the deprived eye. Importantly, the potentiation

of visual responses generalized to novel stimuli without modifying stimulus

selectivity. Subsequent repetitive performance of a two-choice spatial frequency

discrimination task, promoted a recovery of orientation selectivity and spatial

acuity. The combination of dark exposure (to reactivate plasticity), visual tetanus

(to promote synaptic strength) and perceptual learning (to promote neuronal

stimulus selectivity) may accelerate and enhance recovery of visual functions,

thereby optimizing the recovery from severe amblyopia.