Synaptic plasticity in young versus aged cortex

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Project Summary The decline in synaptic plasticity with age is thought to impose severe constraints on the recovery from amblyopia in adults. Although this developmental loss was previously thought to be irreversible, our previous work established that robust plasticity can be reactivated in the adult visual cortex via visual deprivation by dark exposure. Furthermore, dark exposure followed by instructive visual experience enables complete recovery from severe amblyopia in adulthood. Our previous work assumed that the elimination of visual input during dark exposure was sufficient to reactivate plasticity. However, our preliminary data demonstrate that light reintroduction after dark exposure is responsible for the reactivation of structural and functional plasticity in the adult mouse visual cortex. We propose to show that LRx following dark exposure increases the activity of a key extracellular protease (matrix metalloprotease-9) at thalamic inputs to cortical neuron and a counter- intuitive decrease in the excitability of regular spiking neurons to reactivate robust plasticity in the adult dark- exposed cortex.