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.

抽象的 连续的睡眠损失降低了整个大脑和身体系统的生理，最终导致 死亡。为了防止这些后果，稳态机制在长时间醒来后激活以促进 睡觉。了解控制睡眠体内平衡的神经机制将提供对基本的洞察力 睡眠功能并帮助开发为睡眠损失提供弹性的干预措施，但这些 电路尚未清楚地表征。先前的研究已经确定了少量的蝇神经元 该项目进入背面扇形车身（DFB），并充当睡眠的体内稳态控制中心。我们有 进行了RNAi屏幕以识别促进睡眠的DFB输入信号，并表征了输出 DFB神经元释放的信号诱导睡眠。在此提案中，我们将：（1）使用电生理学以及 受体RNAI和突变体确认DFB输入信号身份，（2）为后突触创建遗传记者 DFB神经元的靶标，（3）使用贴片钳记录来测试DFB兴奋性是否升高到 在记忆合并过程中促进睡眠，并在老年苍蝇中降解，导致睡眠破碎。