Neuroendocrine modulation of sleep under starvation stress in Drosophila

睡眠和进食都是生命不可缺少的，都是为了自己的需要而严格控制的。然而，这些基本行为是相互排斥的，因此它们的监管过程相互影响很大。睡眠不足会刺激食欲，而食物匮乏则会抑制睡眠。阐明睡眠和进食之间相互作用的基本机制具有非常重要的意义，因为它有望为动物有效地适应外部环境和内部状态变化而调整其行为的基本原则提供见解。这项研究的重点是类固醇激素及其在饥饿诱导的睡眠抑制(SISS)中的参与，SISS是一种进化上保守的对饥饿的行为反应。鉴于所研究的分子成分(类固醇、多巴胺和G蛋白偶联受体)以及感兴趣的适应性行为(SISS)的普遍重要性，这项研究的结果有望对行为神经内分泌学领域做出重要的总体贡献。该项目还将为本科生提供独特的培训机会，重点是通过少数族裔和研究生的参与扩大参与，并促进针对当地学生和普通公众的外展活动。该项目以果蝇--黑腹果蝇为模型系统，研究内分泌系统如何调节神经系统来控制睡眠和进食。这项研究将阐明G蛋白偶联受体多普埃克受体如何与神经调节剂相互作用，在与饥饿相关的压力下控制睡眠。中心假说是，在饥饿的情况下，多巴胺作用于多巴ECR，通过降低表皮生长因子受体(EGFR)信号的强度来抵消蜕皮激素对多巴ECR的影响，进而诱导SISS。这一假说将通过两个特定的目标来验证：1)确定多巴ECR在调节SISS中作用的关键部位，2)确定蜕皮激素、多巴胺和EGFR信号在多巴ECR介导的SISS中的作用。PI研究小组的初步研究表明，果蝇多巴ECR是一种独特的G蛋白偶联受体(GPCR)，对主要昆虫类固醇激素蜕皮激素和儿茶酚胺多巴胺都有反应，在SISS中起着关键作用。本研究将确定在调节SISS中的关键解剖部位，并确定蜕皮激素和多巴胺在多巴ECR介导的SISS中的作用和机制。

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.