Mechanisms of arousal threshold and sleep homeostasis

项目摘要 当我们入睡时，我们周围的世界不会停止产生刺激。准备 睡觉时，大多数动物都会寻找一个隐蔽的地方，这样不仅可以保护它们免受捕食者的伤害，而且 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，大脑本身也会在睡眠期间过滤信息。我们建议 通过研究睡眠期间感觉信息是如何被门控的，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 它利用了果蝇睡眠时的动态唤醒阈值，果蝇是一种强大的 神经系统功能的遗传解剖模型。我们将寻找基因和神经元 在睡眠过程中控制感觉信息。 果蝇的睡眠表现出哺乳动物睡眠的许多特征，并且已知的睡眠 苍蝇和我们之间的因子是保守的。我们将用苍蝇来理解另一个谜题 这让我们很感兴趣--动物如何调节它们的睡眠时间。我们都熟悉昏昏欲睡的人 当我们只想爬回床上时，这种感觉是由于睡眠不足造成的。这个 对睡眠的需求可能会令人不知所措，这是由于这种行为的本质。但 这种感觉是什么，它从何而来？尽管长期以来人们对这个问题感兴趣，但我们 我对睡眠的动态平衡--生理平衡--没有任何机械的见解 在醒着和睡着之间--是有规律的。使用我们设计的相同系统来探测唤醒 门槛，我们可以剥夺苍蝇的睡眠在高吞吐量和自动化的方式，并期待 对于睡眠不正常的动物来说。我们的方法特别创新 在使用同一系统研究两个不同但基本的生物学问题时。查找 没有感觉到失眠或不能做出充分反应的动物，将负担得起 有机会研究与睡眠稳态有关的分子和神经因素。这真是太棒了 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.