Neuroendocrine modulation of sleep under starvation stress in Drosophila

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Sleep and feeding are both indispensable for life and are strictly controlled for their own need. However, these essential behaviors are mutually exclusive, and therefore their regulatory processes significantly influence one another. Sleep loss leads to stimulation of appetite, and food deprivation leads to a suppression of sleep. Elucidation of the basic mechanisms underlying these interactions between sleep and feeding is highly significance, as it is expected to provide insights into fundamental principles by which animals efficiently adapt their behaviors in response to changes in external environments and internal states. The focus of the study is on steroid hormones and their involvement in starvation-induced sleep suppression (SISS), an evolutionarily conserved behavioral response to starvation. The outcome of this research is expected to make an important general contribution to the field of behavioral neuroendocrinology, given the universal importance of the molecular components studied (steroids, dopamine and G-protein coupled receptor), and the adaptive behavior of interest (SISS). The project will also provide unique training opportunities for undergraduate, with an emphasis on broadening participation through involvement of underrepresented minorities, as well as graduate students and promote outreach activities targeting local students and general public.This project uses the fruit fly, Drosophila melanogaster as a model system and investigates how the endocrine system regulates the nervous system to control sleep and feeding. The research will elucidate how the G-protein coupled receptor DopEcR interacts with neuromodulators to control sleep under the stress associated with starvation. The central hypothesis is that dopamine acts on DopEcR in the context of starvation, counteracting the effects of ecdysone on DopEcR by reducing the strength of epidermal growth factor receptor (EGFR) signaling, and that this in turn induces SISS. This hypothesis will be tested through two specific aims: 1) Identify the critical sites of DopEcR action in regulating SISS, and 2) Determine the roles of ecdysone, dopamine and EGFR signaling in DopEcR-mediated SISS. Preliminary studies in the PI's group have revealed that Drosophila DopEcR, a unique G-protein coupled receptor (GPCR) that responds to both the major insect steroid hormone ecdysone and the catecholamine dopamine plays a critical role in SISS. The study will identify the critical anatomical sites of DopEcR action in regulating SISS, and determining the roles and mechanisms of ecdysone and dopamine in DopEcR-mediated SISS.