SLOW WAVE SLEEP--CONTROL BY THERMOREGULATORY NEURONS

拟议的研究将评估假设的要素，在该假设中 哺乳动物慢波睡眠(SWS)被理解为体温调节过程 这主要受下丘脑体温调节活动的控制。 神经元。视前区催眠机制的存在 下丘脑前区(POAH)及其邻近的基底前脑 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 通过一个功能温度‘设定点’。我们假设POAH 催眠输出由温度敏感神经元的子集控制 引起脑电、荷尔蒙、自主神经和运动活动的变化 集成温度调节响应，产生热量损失，减少 代谢率。这些神经元被假设为编码持续时间 并整合睡眠的昼夜节律和体内平衡控制 通过热敏感度的动态变化。 在行为动物中使用神经元单位记录技术，POAH 将对温度敏感神经元进行鉴定和重新测试 结合脑电-睡眠变量。拟议的研究将评估 一系列关于催眠神经元子集的预测， 基于一个定量的温度调节模型。我们预测 热敏感度将1)随着清醒时间的延长而增加，即， 睡眠不足，2)随着睡眠时间的延长而减少，3)增加 持续的下丘脑增温，4)持续的下丘脑 降温，5)与脑电频谱确定的睡眠深度相关 分析，6)并增加IL-1(与消炎痛联合使用)和 PGD2。催产性冷敏感神经元将表现出相反的变化。 关键的温度敏感神经元将与基底细胞有独特的联系 前脑和脑干系统。此外，持续的下丘脑 变暖和降温将分别增加和减少，随后 睡吧。这些研究将为分类提供一种模式 前面所述的温度敏感型神经元亚型。 发展SWS是体温调节过程的假说将 为睡眠动态平衡分析提供依据，类似于隔离 其他动态平衡系统的关键反馈信号，如血气 在呼吸生理学方面。这种方法将适用于神经和 对鸟类和哺乳动物(包括人类)睡眠的行为研究，并将 对于理解以以下特征为特征的一系列障碍具有重要意义 SWS丢失，包括抑郁和嗜睡症，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.