Plasticity of cortical networks during learning

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PROJECT SUMMARY: Plasticity occurs in the primary visual cortex (V1) in response to visual associative learning, where one stimulus is paired with reward (CS+) and another is not (CS-). However, learning is not a unitary process, and distinct stages of learning might drive contrasting plastic changes in V1. Indeed, previous work has found dynamic changes in V1 pyramidal neuron activity and inputs at different times throughout learning. Experiments separating distinct learning phases behaviorally are lacking, making it difficult to fully dissect V1 plasticity changes throughout learning. To address this, we have designed a 3-phase associative learning task that separates early, stimulus non-specific learning from late, stimulus-specific learning and reversal learning. We will also manipulate stimulus value in two ways: devaluation and spout removal. Using this behavioral paradigm along with 1- and 2-photon calcium imaging of the mouse dorsal cortex, we will test the following hypotheses: 1) that visual associative learning differentially recruits V1 activity during distinct learning stages, 2) activity in V1 is rapidly plastic in response to changes in stimulus value, 3) individual V1 neurons exhibit bidirectional plasticity across learning, 4) visual associative learning changes cortico-cortical functional connectivity, and 5) V1 activity is required to maintain these cortico-cortical functional connectivity changes. Our results will provide an unprecedented level of insight into V1 plasticity throughout learning and stimulus value manipulation. We will, for the first time, address how plasticity in V1 is mirrored across the dorsal cortex, or required for cortico-cortical plasticity.