Notch-dependent microcircuit regulation of alcohol reward memory

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PROJECT SUMMARY Despite its devastating impact on society, there are few effective treatments currently available for alcohol use disorder. The persistence of memories for the intoxication experience induces cravings, which can trigger relapse to alcohol use in recovering individuals. The neural and molecular mechanisms underlying these memories are complex, and despite recent advances, not well understood. This makes progress in finding pharmacological targets challenging. Investigation of these memories in the fruit fly, Drosophila melanogaster, presents a unique opportunity to gain a comprehensive understanding of the memories for alcohol reward at the level of genes, molecules, neurons and circuits. We propose to: 1) identify and investigate how simple central brain circuits function to form memories of the rewarding experience of alcohol intoxication, 2) compare how these circuits function for different forms of reward memory. Specifically, this research will reveal how dopaminergic microcircuits function to assign the rewarding properties of alcohol to associated cues, and how Notch signaling mediates neuronal plasticity within this circuit. This will be informative for understanding basic neural and molecular mechanisms underlying memory formation in addition to investigating how alcohol co-opts the brain's natural reward-related memory mechanisms to result in alcohol cravings.