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.
|Advisor:||Quinlan, Elizabeth M.|
|Commitee:||Araneda, Ricardo C., Hatfield, Bradley D., Lee, Hey-Kyoung, Roesch, Matthew R.|
|School:||University of Maryland, College Park|
|School Location:||United States -- Maryland|
|Source:||DAI-B 74/08(E), Dissertation Abstracts International|
|Subjects:||Ophthalmology, Developmental biology|
|Keywords:||Amblyopia, Monocular deprivation, Ocular dominance, Plasticity|
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