Investigating the logic of homeostatic sleep control circuitry in Drosophila

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Abstract Continuous sleep loss degrades the physiology of systems throughout the brain and body, eventually causing death. To prevent these consequences, homeostatic mechanisms activate after prolonged waking to promote sleep. Understanding neural mechanisms that control sleep homeostasis will provide insight into the basic functions of sleep and aid the development of interventions that provide resilience to sleep loss, but these circuits have not been clearly characterized. Previous studies have identified a small population of fly neurons that project into the dorsal Fan-shaped Body (dFB) and act as a homeostatic control center for sleep. We have conducted an RNAi screen to identify sleep-promoting dFB input signals and have characterized an output signal released by dFB neurons to induce sleep. In this proposal, we will: (1) use electrophysiology along with receptor RNAis and mutants to confirm dFB input signal identity, (2) create genetic reporters for post-synaptic targets of dFB neurons, and (3) use patch-clamp recordings to test whether dFB excitability is elevated to promote sleep during memory consolidation and degraded in aged flies, resulting in sleep fragmentation.