Project Summary Processing of sensory experience, which is essential for navigating and interacting with the world, relies heavily on feedback inputs from higher-order cortical areas. This is further emphasized in the visual system where the connectivity between higher-order visual areas and the primary visual cortex (V1) provides context to the information we see, and allows us to pay attention to important aspects of the visual stimuli. It is well documented that V1 undergoes plastic changes in response to altered visual experience. For instance, in response to visual deprivation, V1 adapts by changing the strength of its connections in a layer specific manner. More specifically, our lab has shown that after visual deprivation, lateral connections in layer 2/3 increase in strength without changes in feedforward connections from layer 4. These changes were readily observed in adult mice, which suggests that visual deprivation is an effective means to produce plasticity in the adult brain. Feedback projections from higher-order visual areas constitute one of the major lateral inputs to V1 layer 2/3 neurons. Visual deprivation-induced plasticity has been studied extensively in V1, but whether and how higher-order visual areas adapt to changes in visual experience is currently unknown. I propose to fill this knowledge gap by first investigating if the strength of the dense feedback projections from higher-order visual areas into V1 layer 2/3 is increased after visual deprivation (Aim1). Additionally, inhibitory circuitry is important in modulating responses of neurons and provides another way of controlling plasticity. I will investigate the connections between higher-visual areas and inhibitory cells in V1 layer 2/3 and determine how vison loss changes the strength of these connections (Aim2). Lastly, I will investigate how loss of these feedback projections affects the spontaneous activity of neurons in V1 layer 2/3 (Aim 3). The results obtained from this work will shed light on how inputs from higher-order visual areas to V1 adapt to the loss of vision, and how these inputs contribute to spontaneous activity in V1. Furthermore, because my proposed study will be done in adults, the results will provide mechanistic understanding on the innate plasticity in the adult visual system, and provide us with potential targets to promote V1 plasticity that could compensate for loss of visual function.