Sleep control by the preoptic area of the hypothalamus

项目摘要 睡眠是动物界广泛观察到的一种基本行为。睡眠的特点是 在快速眼动（REM）和非REM（NREM）睡眠之间重复的大脑状态转换。睡眠 它们之间的状态和转换由神经元群体之间的相互作用调节， 自我平衡的需要目前，我们对控制睡眠的大脑机制缺乏详细的了解。的 下丘脑的视前区对睡眠控制至关重要，包含在睡眠期间活跃的神经元 这是睡眠所必需的。其中一个挑战是唤醒、快速眼动和非快速眼动活跃的神经元是混合在一起的 在视前区，使其难以专门针对REM和NREM活动神经元的电路 分析.我们以前的研究表明，表达胆囊收缩素或促肾上腺皮质激素的视前神经元亚群- 释放激素促进REM和NREM睡眠，而表达速激肽1的神经元促进REM睡眠。 NREM睡眠这些发现为探索视前睡眠的作用提供了一个有价值的切入点 控制REM和NREM睡眠的回路，大脑状态转换和两种睡眠的稳态调节 states.在目标1中，我们将研究电路机制，以了解这些视前神经元的子集 通过与下游靶点的相互作用调节REM和NREM睡眠。在目标2中，我们将 研究视前睡眠神经元如何整合稳态压力以响应REM的机制 NREM睡眠缺失实现这些目标将提供重要的电路水平的见解，神经 睡眠调节的基础，与理解和开发新的治疗干预措施具有潜在的相关性 治疗睡眠障碍

PROJECT SUMMARY Sleep is a fundamental behavior that is widely observed across the animal kingdom. Sleep is characterized by repeated brain state transitions between rapid eye movement (REM) and non-REM (NREM) sleep. Sleep states and transitions between them are regulated by reciprocal interactions between neuronal populations and homeostatic need. At present, we lack detailed understanding of the brain mechanisms controlling sleep. The preoptic area of the hypothalamus is crucial for sleep control and contains neurons that are active during sleep and are necessary for sleep. One challenge is that wake, REM and NREM-active neurons are intermingled within the preoptic area, making it difficult to specifically target REM and NREM-active neurons for circuit analysis. We previously showed that subsets of preoptic neurons expressing cholecystokinin or corticotropin- releasing hormone promote both REM and NREM sleep whereas tachykinin 1 expressing neurons promote only NREM sleep. These findings serve as a valuable entry point for exploring the role of the preoptic sleep circuitry in controlling REM and NREM sleep, brain state transitions and homeostatic regulation of both sleep states. In Aim 1, we will investigate circuit mechanisms to understand how these subsets of preoptic neurons regulate REM and NREM sleep through their interactions with downstream targets. In Aim 2, we will investigate the mechanisms how preoptic sleep neurons integrate homeostatic pressure in response to REM and NREM sleep loss. Accomplishing these aims will provide important circuit-level insights into the neural basis of sleep regulation, with potential relevance to understand and develop novel therapeutic interventions for sleep disorders.