Mechanisms of arousal threshold and sleep homeostasis

觉醒阈值和睡眠稳态的机制

• 批准号: 9165436
• 负责人: Dragana Rogulja
• 金额: $ 254.25万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9165436
• 关键词: Animals; Arousal; Awareness; Back; Beds; Behavior; Behavioral; Biological; Biological Phenomena; Brain; Characteristics; Delayed Sleep Phase Syndrome; Diabetes Mellitus; Dissection; Drosophila genus; Drosophila melanogaster; Equilibrium; Feeling; General Population; Genes; Genetic Models; Health; Homeostasis; Homologous Gene; Human; Link; Malignant Neoplasms; Mental Depression; Molecular; Narcolepsy; Nature; Nervous System Physiology; Neurons; Role; Sensory; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep disturbances; Spottings; Stimulus; System; casein kinase I; design; falls; fly; innovation; insight; interest; neural correlate; novel; sensory gating; sleep regulation

Project Summary When we fall asleep, the world around us doesn't stop producing stimuli. Preparing for sleep, most animals seek out a secluded spot that not only protects them from predators, but also helps filter out some of the sensory information that is constantly bombarding our senses. In addition to this behavioral filtering, the brain itself filters information during sleep. We propose that by studying how sensory information is gated during sleep, we can gain insight into how sensory awareness is generated in the brain. We are establishing novel experimental platforms that exploit the dynamic arousal threshold during sleep in Drosophila melanogaster, a powerful model for the genetic dissection of nervous system function. We will look for genes and neurons that gate sensory information during sleep. Sleep in Drosophila displays many characteristics of mammalian sleep, and known sleep factors are conserved between flies and us. We will use the fly to understand another puzzle that interests us - how animals regulate their sleep amount. We are all familiar with the drowsy feeling that results from inadequate sleep, when all we want to do is crawl back to bed. The need for sleep can be overwhelming, and this is due to the essential nature of this behavior. But what is this feeling, where does it come from? Despite longstanding interest in this question, we do not have any mechanistic insights into how sleep homeostasis – the physiological balance between waking and sleep - is regulated. Using the same system we designed to probe arousal threshold, we can deprive flies of sleep in a high-throughput and automated manner, and look for animals whose rebound sleep deviates from normal. Our approach is particularly innovative in using the same system to study two distinct but essential biological questions. Finding animals that do not sense the loss of sleep, or cannot respond adequately, will afford an opportunity to study molecular and neural correlates of sleep homeostasis. This is of great relevance for human health, as sleep disturbances underlie many significant health problems including depression, diabetes and cancer.

项目总结

项目成果

A gut-secreted peptide suppresses arousability from sleep.

肠道分泌的肽会抑制睡眠中的觉醒。

• DOI: 10.1016/j.cell.2023.04.005
• 发表时间: 2023
• 期刊: Cell
• 影响因子: 64.5
• 作者: Titos,Iris;Juginović,Alen;Vaccaro,Alexandra;Nambara,Keishi;Gorelik,Pavel;Mazor,Ofer;Rogulja,Dragana
• 通讯作者: Rogulja,Dragana