Investigating the logic of homeostatic sleep control circuitry in Drosophila

研究果蝇稳态睡眠控制电路的逻辑

• 批准号: 10356170
• 负责人: Jeffrey Michael Donlea
• 金额: $ 34.13万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10356170
• 关键词: Acute; Age; Aging; Allatostatin; Anatomy; Arousal; Biological Models; Brain; Cause of Death; Cell physiology; Cells; Chronic Disease; Cognitive deficits; Diabetes Mellitus; Dissection; Dorsal; Drosophila genus; Electrophysiology (science); G-Protein-Coupled Receptors; Genetic; Genetic Heterogeneity; Homeostasis; Human; Hypertension; Intervention; Label; Ligands; Logic; Maps; Measures; Modeling; Neurons; Neuropeptides; Organism; Output; Physiology; Population; RNA Interference; RNA interference screen; Reporter; Research; Rest; Risk; Rodent; Role; Signal Transduction; Sleep; Sleep Deprivation; Sleep Fragmentations; Sleep disturbances; Sleeplessness; Starvation; Synapses; System; Testing; Time; Vertebrates; Whole-Cell Recordings; Work; age related; aged; cell type; experience; fly; genetic manipulation; genomic locus; improved; insight; memory consolidation; mutant; neurochemistry; neuromechanism; neuroregulation; novel; patch clamp; physiologic stressor; pressure; prevent; promoter; public health relevance; receptor; resilience; response; sleep regulation; therapy development

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.

摘要 持续的睡眠不足会降低大脑和身体各个系统的生理功能，最终导致 死亡。为了防止这些后果，体内平衡机制在长时间清醒后激活，以促进 睡吧。了解控制睡眠动态平衡的神经机制将提供对基础睡眠的洞察 睡眠的功能，并帮助开发干预措施，提供对睡眠损失的弹性，但这些 电路还没有被清楚地描述出来。以前的研究已经发现了一小部分果蝇神经元 它投射到背部扇形身体(DFB)，充当睡眠的动态平衡控制中心。我们有 已进行RNAi屏幕以识别促进睡眠的DFB输入信号，并已表征输出 DFB神经元释放的诱导睡眠的信号。在这项建议中，我们将：(1)使用电生理学和 受体RNA和突变体以确认DFB输入信号的身份，(2)创建突触后的遗传报告 DFB神经元的靶，以及(3)使用膜片钳记录来测试DFB的兴奋性是否升高到 在记忆巩固期间促进睡眠，并在老年果蝇中降解，导致睡眠碎片化。