Recovering plasticity in adult ferret V1 by cross-modal deprivation

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 DESCRIPTION (provided by applicant): Long-term monocular deprivation (MD) initiated before any visual experience leads to permanent loss of vision through the occluded eye, and is much more resistant to recovery later in life compared to MD initiated after a period of normal vision. At a functional and anatomical level, it is known that long-term MD leads to a shift in ocular dominance (OD) in the primary visual cortex (V1). In particular, V1 neurons lose responses from the deprived eye, which are thought to result from mechanisms resembling long-term depression (LTD). While recent studies have reported recovery from long-term MD using either genetic manipulations or invasive pharmacological interventions, these cases have been limited to long-term MD after about a week of normal vision during early development. Studies have shown that MD initiated before eye opening in diverse animal models is much more resilient to recovery, and is thought to involve changes in thalamocortical (TC) inputs to V1. Hence methods to recover plasticity at TC synapses would benefit recovery from chronic long-term MD without initial vision. We recently found that deafening adult mice for a brief duration leads to potentiation of TC synapses in layer 4 (L4) of V1. Here we propose to examine whether deafening adult ferrets for a brief duration would allow cross-modal potentiation of TC synapses in V1 to promote recovery from chronic long-term MD initiated before eye opening. Ferret V1 is organized similar to humans with OD columns and orientation pinwheels, which overcomes the limits of mouse V1 lacking such modular organization. To test our hypothesis that deafening promotes TC plasticity in adult ferret V1, we will utilize channelrhodopsin based optogenetic tools to quantitatively measure the strength of TC synapses in L4 of V1 with or without deafening (Aim 1). In addition, intracortical synaptic strength in L4 will be quantified. T investigate whether cross-modal potentiation of TC synapses promotes recovery from chronic long-term MD, we will compare V1 neuronal functions, including OD and visual acuity, using multi-site laminar recording probes (Aim 2). The results from our study will determine whether cross-modal sensory deprivation in adults would promote recovery from chronic long-term MD by restoring TC plasticity. Our results could be generalized to promote recovery from sensory loss in other modalities, and pave a way to develop non-invasive means to recover from deprivation amblyopia in adults.