Mechanisms of arousal threshold and sleep homeostasis

项目摘要 当我们入睡时，我们周围的世界并没有停止产生刺激。准备 睡觉时，大多数动物会寻找一个隐蔽的地方，不仅保护它们免受捕食者的伤害， 也有助于过滤掉一些不断轰炸我们感官的感官信息。 除了这种行为过滤之外，大脑本身也在睡眠中过滤信息。我们提出 通过研究感觉信息在睡眠中是如何被门控的，我们可以深入了解 感官意识是在大脑中产生的。我们正在建立新的实验平台 利用黑腹果蝇睡眠期间的动态唤醒阈值， 神经系统功能的遗传解剖模型。我们将寻找基因和神经元 在睡眠中控制感官信息的神经系统 果蝇的睡眠表现出哺乳动物睡眠的许多特征， 在苍蝇和我们之间是保守的。我们将用苍蝇来理解另一个谜题 动物是如何调节睡眠量的我们都熟悉昏昏欲睡的人 这种感觉是由于睡眠不足造成的，我们只想爬回床上。的 对睡眠的需求可能是压倒性的，这是由于这种行为的本质。但 这种感觉是什么，从何而来？尽管对这个问题的兴趣由来已久， 我对睡眠的稳态--生理平衡--没有任何机械的见解， 在清醒和睡眠之间-是受调节的。用的是我们设计的探测唤醒的系统 阈值，我们可以以高通量和自动化的方式剥夺苍蝇的睡眠， 对于那些反弹睡眠偏离正常的动物来说。我们的方法特别创新 使用同一个系统来研究两个不同但重要的生物学问题。找到 没有感觉到睡眠丧失或不能充分反应的动物， 有机会研究睡眠稳态的分子和神经相关性。具有重大 与人类健康相关，因为睡眠障碍是许多重大健康问题的基础 包括抑郁症糖尿病和癌症

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.