Gender-dimorphic Regulation of Sleep

 描述(申请人提供)：睡眠是一种基本的生物学过程，从苍蝇到人类都是如此。对睡眠调节的研究主要集中在两个主要机制上：控制何时睡眠的昼夜节律机制和调节睡眠时间长短的稳态机制。尽管如此，性别等其他因素也会影响睡眠，但性别二态睡眠调节背后的机制却鲜为人知。这项提议旨在研究一种新的果蝇神经回路，该回路涉及雄性特有的睡眠调节。我们最近在大脑中发现了少量神经元，它们的激活会导致雄性果蝇睡眠显著减少，但在雌性果蝇中没有。真令人兴奋 因为尽管已经在果蝇中发现了几个睡眠调节神经元中心，但这是性别二态唤醒中心的第一个例子。我们的初步数据表明，新发现的觉醒中心在女性在场的情况下促进觉醒，并与表达男性特有的转录因子Fruitless M的神经元进行突触接触，这是男性求爱行为所必需的。为了理解这个新的唤醒中心是如何以性别二态的方式调节睡眠的，需要解决几个关键问题。这个神经中枢的输入信号和行为输出是什么？神经中心还连接到哪些其他神经元群体，它使用的是哪种神经传递系统？我们将使用一系列可用于果蝇电路分析的遗传工具来解决这些问题。这项工作将研究一种新的神经回路，涉及男性特有的睡眠调节，并将为理解睡眠中的性别差异提供新的研究途径。此外，这项工作可能会为大脑如何平衡决定适当行为的竞争需求这一根本问题提供有价值的见解。

 DESCRIPTION (provided by applicant): Sleep is an essential biological process that is conserved from flies to humans. Studies of sleep regulation have focused on two main mechanisms: the circadian mechanism that controls when to sleep and the homeostatic mechanism that regulates how much to sleep. Nevertheless, other factors, such as gender, also affect sleep, but the mechanism underlying gender-dimorphic sleep regulation is poorly understood. This proposal aims to investigate a novel Drosophila neural circuit involved in male-specific regulation of sleep. We recently identified a small number of neurons in the brain whose activation leads to markedly reduced sleep in male flies, but not in female flies. This is exciting because although several sleep-regulatory neuronal centers have been identified in Drosophila, this is the first example of a gender-dimorphic arousal center. Our preliminary data suggest that the newly identified arousal center promotes wakefulness in the presence of females and makes synaptic contacts with neurons that express the male-specific transcription factor FruitlessM, which is required for male courtship behavior. To understand how this novel arousal center regulates sleep in a gender-dimorphic manner, several key questions need to be addressed. What are the input signals and behavioral outputs of this neural center? What other neuronal populations does the neural center connect to and which neurotransmission system does it employ? We will address these questions using an array of genetic tools that are available for circuit analysis in Drosophila. This work will investigate a novel neural circuit involved in male-specific regulation of sleep and will produce new research avenues for understanding sex differences in sleep. Further, this work may provide valuable insights into the fundamental problem of how the brain balances competing needs to decide on appropriate behaviors.