Integration of sleep-regulating signals by the Drosophila Pars Intercerebralis

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 DESCRIPTION (provided by applicant): Although sleep is a fundamental process involved in survival and proper brain performance, how the brain determines when to fall asleep and wake up is still not understood. The importance of sleep is further underscored by accumulating evidence that sleep deprivation and circadian rhythm disruption contributes to chronic health issues, due to the role of sleep in many physiological processes including metabolism, immune function, memory consolidation and more. Sleep results from the sum of information from two systems: the circadian clock and the sleep homeostatic system. The circadian system contains a core molecular clock that is synchronized to the time of day by visual inputs and drives a 24h rhythm in many physiological processes and behaviors, including sleep. The sleep homeostasis system signals the need to sleep after prolonged wakefulness. How and where homeostatic and circadian information are integrated to drive sleep is not known. The central hypothesis of this proposal is that the Pars Intercerebralis (PI), an analog of the mammalian hypothalamus, receives and integrates both circadian and homeostatic information. The PI is involved in controlling both amount of sleep, which is a measure of the homeostatic system, as well as circadian timing of sleep. The PI is part of a circadian output pathway controlling rest-activity rhythms and likely receives input from multiple areas, including the core circadian clock and regions involved in sleep homeostasis. PI output is largely in the form of peptides released from distinct PI cell populations. These peptide signals may have diverse targets inside and outside the nervous system. The aims of this project are 1) To determine whether the firing of PI cells reflects circadian control; 2) To determine whether the firing behavior of PI cells is also affecte by the sleep homeostat and 3) To map the putative interactions of circadian and homeostatically controlled PI cells. To pursue these aims, a combination of Drosophila genetics and behavior, electrophysiology and calcium imaging will be used. Understanding the neural circuits involved in making sleep-wake decisions will open the door to novel hypotheses of how to influence these decisions to aid in healthy sleep and disease prevention.