Investigating the logic of homeostatic sleep control circuitry in Drosophila

摘要 持续的睡眠不足会降低整个大脑和身体的生理系统，最终导致 死亡为了防止这些后果，稳态机制在长时间清醒后激活， 睡吧了解控制睡眠稳态的神经机制将有助于深入了解睡眠的基本机制。 睡眠的功能，并帮助干预措施的发展，提供弹性睡眠损失，但这些 电路还没有被清楚地表征。以前的研究已经确定了一小群苍蝇神经元 投射到背侧扇形体（dFB），作为睡眠的自我平衡控制中心。我们有 进行RNAi筛选以识别促进睡眠的DFB输入信号，并表征输出 通过dFB神经元释放信号以诱导睡眠。在本建议中，我们将：（1）使用电生理学沿着 受体RNAi和突变体，以确认DFB输入信号的身份，（2）创建用于突触后的遗传报告基因， dFB神经元的靶点，以及（3）使用膜片钳记录来测试dFB兴奋性是否升高到 在记忆巩固期间促进睡眠，在老年苍蝇中退化，导致睡眠碎片。

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.