SLOW WAVE SLEEP--CONTROL BY THERMOREGULATORY NEURONS

拟议的研究将评估假设的要素，其中 哺乳动物慢波睡眠被认为是一种体温调节过程 它主要由下丘脑温度调节的活动控制， 神经元 视前区催眠机制的存在 下丘脑前区（POAH）和邻近的基底前脑已经被 由神经元单位记录、刺激和损伤支持 方法论。 其他证据表明，催眠和 POAH的体温调节功能是紧密结合和调节的 通过功能温度"设定点"。 我们假设POAH 催眠输出是由一部分热敏神经元控制的 其引起EEG、激素、自主神经和运动活动的变化， 综合性体温调节反应，产生热量损失， 代谢率 这些神经元被假设编码的持续时间 以及整合睡眠的昼夜节律和自我平衡控制 通过热敏性的动态变化。 在行为动物的神经元单位记录技术， 温敏神经元将被识别并按顺序重新测试， 结合脑电图睡眠变量。 拟议的研究将评估 一系列关于假定催眠神经元子集的预测， 基于定量体温调节模型。 我们预测 温敏感性将1）随着清醒时间的延长而增加，即， 睡眠剥夺，2）随着睡眠时间的延长而减少，3）随着睡眠时间的延长而增加， 持续的下丘脑变暖，4）随着持续的下丘脑 冷却，5）与睡眠深度相关，如通过EEG频谱 分析，6）和增加IL-1（与吲哚美辛组合）， PGD 2. 而催眠状态下的冷敏感神经元则表现出相反的变化。 关键的温度敏感神经元与基底神经元有着独特的联系， 前脑和脑干系统。 此外，持续的下丘脑 变暖和变冷将分别增加和减少，随后 睡吧 这些研究将提供一个模型， 先前描述的温敏神经元亚型。 SWS是一个体温调节过程的假设的发展， 为睡眠稳态的分析提供了基础，类似于分离 用于其它稳态系统的关键反馈信号 在呼吸生理学上。 这种方法适用于神经和 对鸟类和哺乳动物（包括人类）睡眠的行为研究， 对于理解一系列疾病具有重要意义， SWS丧失，包括抑郁症和嗜睡症，以及睡眠的影响 剥夺

The proposed studies will evaluate elements of a hypothesis in which mammalian slow wave sleep (SWS) is understood as a thermoregulatory process that is controlled primarily by activity of hypothalamic thermoregulatory neurons. The existence of hypnogenic mechanisms in the preoptic area-anterior hypothalamus (POAH) and adjacent basal forebrain has been supported by neuronal unit recording, stimulation, and lesion methodologies. Other evidence shows that the hypnogenic and thermoregulatory functions of the POAH are closely integrated and regulated by a functional temperature 'set point". We hypothesize that the POAH hypnogenic output is controlled by a subset of thermosensitive neurons which induce changes in EEG, hormonal, autonomic, and motor activity as an integrated thermoregulatory response, producing heat loss and reduced metabolic rate. These neurons are hypothesized to encode the duration of prior waking and to integrate circadian and homeostatic controls of sleep through dynamic changes in thermosensitivity. With neuronal unit recording techniques in behaving animals, POAH thermosensitive neurons will be identified and retested sequentially in conjunction with EEG-sleep variables. Proposed studies will evaluate a series of predictions concerning a subset of putative hypnogenic neurons, based on a quantitative thermoregulatory model. We predict that warm-sensitivity will be 1) increased with extended time awake, that is, sleep deprivation, 2) decreased with extended time asleep, 3) increased by sustained hypothalamic warming, 4) decreased with sustained hypothalamic cooling, 5) correlated with sleep depth as determined by EEG spectral analysis, 6) and increased by IL-1 (in combination with indomethacin) and PGD2. Hypnogenic cold-sensitive neurons would exhibit opposite changes. Critical thermosensitive neurons would have unique connections to basal forebrain and brainstem systems. In addition, sustained hypothalamic warming and cooling will increase and decrease, respectively subsequent sleep. These studies would provide a model for classification of thermosensitive neuronal subtypes described previously. Development of a hypothesis that SWS is a thermoregulatory process would provide a basis for analysis of sleep homeostasis, analogous to isolating critical feedback signals for other homeostatic systems such as blood gases in respiratory physiology. This approach would be applicable to neural and behavioral studies of sleep in birds and mammals, including man, and would have significance for a understanding a range of disorders characterized by SWS loss, including depression and Narcolepsy, as well as effects of sleep deprivation.