Median Preoptic Nucleus and the Control of Sleep

描述（由申请人提供）：睡眠调节具有体内平衡成分，睡眠剥夺导致的睡眠量和睡眠深度可靠而强劲的增加证明了这一点。虽然在识别伴随睡眠缺失的神经化学和基因表达变化方面取得了进展，但对睡眠调节的稳态方面最重要的神经回路的识别仍然缺乏。在之前的资助期内，我们研究了中视前核（MnPN）和腹外侧视前区（VLPO）神经元的睡眠调节功能。我们证明，与VLPO类似，MnPN包含大量在非快速眼动睡眠和快速眼动睡眠中都被激活的神经元，与清醒相比，MnPN和VLPO睡眠活跃的神经元是gaba能的，并且MnPN投射到涉及觉醒、非快速眼动睡眠和快速眼动睡眠控制的几个大脑区域。我们还证明了MnPN神经元在睡眠剥夺期间被最大限度地激活，VLPO神经元在睡眠剥夺后的恢复性睡眠期间被最大限度地激活。视前区神经元的激活发生在完全睡眠剥夺和选择性快速眼动睡眠剥夺的反应中。后一项研究发现，MnPN和VLPO神经元可能是调节非快速眼动和快速眼动睡眠稳态的神经回路的组成部分。建议的工作将回答以下关键问题：1)单个MnPN和VLPO神经元是否在睡眠剥夺期间随着睡眠需求的积累而逐渐激活，并在恢复睡眠期间随着需求的消散而去激活？2)在睡眠剥夺和恢复性睡眠期间，腺苷能机制是否导致了MnPN和VLPO神经元活动的变化？3)完全睡眠剥夺和选择性REM睡眠剥夺激活的MnPN和VLPO神经元是否投射到不同的脑区？启动和维持睡眠的能力受损是一些精神疾病的一个突出特征，包括抑郁症、创伤后应激障碍和焦虑症。在这些疾病中，非快速眼动和快速眼动睡眠控制都出现失调。拟议的工作将试图描述功能神经解剖学和前脑和脑干神经回路的神经化学调节，这些神经回路是正常和紊乱的稳态睡眠调节的基础。

DESCRIPTION (provided by applicant): The regulation of sleep has a homeostatic component, as evidenced by reliable and robust increases in sleep amount and sleep depth that are a consequence of sleep deprivation. While progress has been made in identifying neurochemical and gene expression changes that accompany sleep loss, identification of neuronal circuits most crucial to homeostatic aspects of sleep regulation is lacking. In the previous funding period, we examined sleep-regulatory functions of neurons in the median preoptic nuclues (MnPN) and ventrolateral preoptic area (VLPO). We demonstrated that, similar to VLPO, the MnPN contains significant numbers of neurons that are activated during both nonREM and REM sleep compared to waking, that MnPN and VLPO sleep-active neurons are GABAergic, and that the MnPN projects to several brain regions implicated in the control of arousal, nonREM sleep and REM sleep. We also demonstrated that MnPN neurons are maximally activated during sleep deprivation and that VLPO neurons are maximally activated during recovery sleep following sleep deprivation. Activation of preoptic area neurons occurs in response to total sleep deprivation as well as in response to selective REM sleep deprivation. These latter findings identify MnPN and VLPO neurons as possible components of neural circuits regulating nonREM and REM sleep homeostasis. Proposed work will answer the following critical questions: 1) Do individual MnPN and VLPO neurons become progressively activated in association with accumulating sleep need during sleep deprivation, and de-activated as that need dissipates during recovery sleep? 2) Are adenosinergic mechanisms responsible for changes in the activity of MnPN and VLPO neurons that occur during sleep deprivation and recovery sleep? 3) Do MnPN and VLPO neurons activated during total sleep deprivation and those activated during selective REM sleep deprivation project to different brain regions? Impaired ability to initiate and maintain sleep is a prominent feature in several psychiatric disorders including, depression, post-traumatic stress disorder and anxiety disorders. Dysregulation of both nonREM and REM sleep control are seen in these diseases. Proposed work will attempt to characterize the functional neuroanatomy and the neurochemical modulation of forebrain and brainstem neural circuits that underlie normal and disordered homeostatic sleep regulation.