Project Summary Learning and memory are modulated by dopaminergic circuits, which convey valence and/or arousal signals. This proposal will examine how discrete dopaminergic circuits modulate learning and memory and neuronal plasticity in memory-encoding brain regions in Drosophila. Specifically, it will disentangle the roles of dopaminergic circuits that convey positive valence signals, negative valence signals, and valence-independent arousal signals. In vivo imaging experiments will examine how these dopaminergic neurons drive discrete patterns of plasticity in the mushroom body and downstream valence-coding output neurons that mediate approach and avoidance behavior. Complementary behavioral and optogenetic manipulation experiments will decipher how each of these neuronal subsets modulates arousal, valence, and memory strength. These studies will apply the large genetic toolkit and experimental throughput of the fly toward developing a more comprehensive understanding of how learning and memory alter the flow of information through the brain, to ultimately engage novel behaviors (e.g., conditioned approach/avoidance) following learning. Understanding how memories are encoded in the brain and disrupted in brain disorders is a prerequisite to the rational design of treatments for memory impairment. Results of the present studies will provide guideposts for future research into the molecular biology of memory formation across multiple model organisms, as dopaminergic circuits regulate arousal and memory across taxa. The project will support our long-term goal of understanding of memory down to the single-cell and subcellular levels, contributing to the knowledge base necessary for the rational development of novel treatments for memory impairment.