SLEEP CONTROL BY THERMOSENSITIVE NEURONS

描述(申请人摘要)：我们建议学习神经生理学 脑内含5-羟色胺神经元的调节机制 哺乳动物中缝背核(DRN)在视前区的催眠系统 下丘脑及邻近基底前脑(POA/BF)。激活期间 温敏神经元的自发睡眠及其失活 冷敏感神经元(CSN)在POA/BF催眠中起关键作用 进程。WSN和CSN由对当地变暖的响应和 正在降温。先前的证据表明，POA/BF也包含这两种 REM-促进和抑制REM的过程。DRN 5-羟色胺能神经元的抑制 神经元放电在非快速眼动睡眠开始和快速眼动中都起作用。 睡眠触发。最近的解剖学和生理学证据表明 激活POA/BF WSN/CSN催眠系统可诱导抑制 DRN神经元活动，提示NREM-REM的机制基础 协调。我们已经开发了一个可测试的DRN调节的两阶段模型 和由POA/BF触发的REM。目标1是量化REM的调节 POA/BF温度敏感神经元对睡眠的控制。目标2是使用 微透析法证实POA/BF升温可导致血管释放增加 DRN中抑制性神经递质，γ-氨基丁酸(GABA)，以及 突触后阻断DRN中的GABA可阻止POA/BF引起的NREM改变 脑电失活和快速眼动触发。目标3将结合微透析和 在DRN记录神经元单位以评估GABA释放的假说 POA/BF加温对DRN神经元放电和DRN的影响 神经元放电调节REM的触发。目标4将使用技术来 快速眼动丰富睡眠的产生及原癌基因c-fos的表达方法 标记神经元活动，以评估一种假设，即 视前腹外侧区(Peri-VLPO)包括 REM选择性神经元。目的5证实REM选择性神经元的存在 在VLPO周围使用慢性神经元单位记录技术。目标6是使用 微透析GABA激动剂苍蝇酚灭活VLPO周围区域以 评估这一区域对快速眼动触发至关重要的假设。这些 研究将提供NREM和REM睡眠相互作用的新模型 机制，并将有助于理解人类疾病，包括 发作性睡病和情感障碍，其中NREM-REM连接紊乱。

DESCRIPTION (applicant's abstract): We propose to study neurophysiological mechanisms mediating the regulation of serotonin-containing neurons in the mammalian dorsal raphe nucleus (DRN) by the hypnogenic system in the preoptic hypothalamus and adjacent basal forebrain (POA/BF). Activation during spontaneous sleep of warm-sensitive neurons (WSNs) and deactivation of cold-sensitive neurons (CSNs) plays a critical role in the POA/BF hypnogenic process. WSNs and CSNs are identified by responses to local warming and cooling. Previous evidence shows that the POA/BF also contains both REM-facilitatory and REM-inhibitory processes. Suppression of DRN serotonergic neuronal discharge was shown to play a role in both NREM sleep onset and REM sleep triggering. Recent anatomical and physiological evidence shows that activation of the POA/BF WSN/CSN hypnogenic system can induce suppression of DRN neuronal activity, suggesting a mechanistic basis for NREM-REM coordination. We have developed a testable 2-stage model of regulation of DRN and REM triggering by the POA/BF. Aim 1 is to quantify the regulation of REM sleep control by POA/BF temperature-sensitive neurons. Aim 2 is to use microdialysis to confirm that POA/BF warming induces increased release of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) in DRN, and that postsynaptic blockade of GABA in DRN prevents POA/BF-induced changes in NREM EEG deactivation and REM-triggering. Aim 3 will combine microdialysis and neuronal unit recording in the DRN to assess hypotheses that GABA release induced by POA/BF warming regulates DRN neuronal discharge and that DRN neuronal discharge regulates REM triggering. Aim 4 will use techniques to generate REM-enriched sleep and the method of proto-oncogene c-fos expression to label neuronal activity in order to assess a hypothesis that a subregion of the POA/BF, the peri-ventrolateral preoptic area (peri-VLPO) contains REM-selective neurons. Aim 5 is confirm the existence of REM-selective neurons in peri-VLPO using chronic neuronal unit recording techniques. Aim 6 is to use microdialysis of a GABA agonist, muscimol, to inactivate the peri-VLPO area to assess the hypothesis that this region is essential for REM-triggering. These studies will provide a new model of interactions of NREM and REM sleep mechanisms and will contribute to the understanding of human diseases including narcolepsy and affective disorder in which NREM-REM coupling is disordered.