Median Preoptic Nucleus and the Control of Sleep

描述（由申请人提供）：睡眠的调节具有稳态成分，如睡眠量和睡眠深度的可靠和稳健的增加所证明的，睡眠量和睡眠深度的增加是睡眠剥夺的结果。虽然在识别伴随睡眠丧失的神经化学和基因表达变化方面取得了进展，但缺乏对睡眠调节的稳态方面最关键的神经元回路的识别。在上一个资助期，我们研究了正中视前核（MnPN）和腹外侧视前区（VLPO）神经元的睡眠调节功能。我们证明，类似于VLPO，MnPN包含大量的神经元，与清醒相比，在非REM和REM睡眠期间被激活，MnPN和VLPO睡眠活性神经元是GABA能的，并且MnPN投射到涉及控制唤醒、非REM睡眠和REM睡眠的几个脑区。我们还证明，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睡眠期间被最大限度地激活。视前区神经元的激活发生在对完全睡眠剥夺以及对选择性REM睡眠剥夺的响应中。这些后者的研究结果确定MnPN和VLPO神经元的神经回路调节nonREM和REM睡眠稳态的可能组成部分。拟议的工作将回答以下关键问题：1）在睡眠剥夺期间，个体MnPN和VLPO神经元是否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失活？2)腺苷能机制是否对睡眠剥夺和恢复睡眠期间MnPN和VLPO神经元活性的变化负责？3)在完全睡眠剥夺和选择性REM睡眠剥夺中激活的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包括抑郁症、创伤后应激障碍和焦虑症在内的几种精神障碍的突出特征。在这些疾病中可以看到非REM和REM睡眠控制的失调。拟议的工作将试图表征功能性神经解剖学和前脑和脑干神经回路的神经化学调制，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.