Synaptic plasticity in young versus aged visual cortex

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DESCRIPTION (provided by applicant): The ability of experience to regulate the cortical function decreases significantly over the lifetime of an animal. During an early, postnatal critical period, monocular deprivation (MD) induces a shift in the ocular dominance (OD) of binocular neurons through a rapid decrease in the strength of synapses serving the deprived eye. In addition, a slower increase in the strength of synapses serving the non-deprived eye is observed. Recent work, by our lab and others, demonstrates that ocular dominance shifts can also be induced in adults, after the classical critical period, however longer periods of MD are required. In adults, deprivation engages only the slow component, increasing the strength of synapses serving the non-deprived input. This demonstrates that OD plasticity persists into adulthood, and suggests the intriguing possibility that opportunities to regulate OD plasticity may also persist throughout lifetime. Our preliminary experiments tested this hypothesis, and demonstrate that visual deprivation, through dark exposure (DE), reactivates rapid juvenile-like OD plasticity in response to monocular deprivation. The OD shift induced after dark exposure is due to a rapid decrease in the strength of synapses serving the deprived eye, previously only described in juveniles, and a rapid increase in the strength of synapses serving the non-deprived eye, which typically develops slowly in juveniles and adults. The proposed experiments examine the temporal requirements and functional consequences of dark exposure, and use a battery of transgenic and pharmacological manipulations to test the hypothesis that dark exposure decreases inhibition in the visual cortex, allowing a return to a more plastic, juvenile-like state. In addition, we test the hypothesis that DE will increase the success of regaining function in an eye deprived of vision from birth. Such a non-invasive method to restore experience-dependent synaptic plasticity in the mammalian cortex holds great therapeutic potential, as the visual deficit resulting from amblyopia in humans is often irreversible by age 10.