NEUROPHYSIOLOGICAL MECHANISMS OF SLEEP CYCLE CONTROL

快速眼动（REM）触发机制的研究 睡眠表明这种行为状态是由激活产生的 脑桥旁正中脑干中的分布式神经元网络 这导致了许多其他神经元的募集， 在整个大脑中。 使用单细胞记录，神经元 连通性映射和显微注射药理学技术， 在描绘触发神经元回路方面取得了相当大的进展， 快速眼动睡眠已被提出，但其长期的调节和功能 其后果仍不清楚。 我们最近发现， 内源性胆碱能臂周肌的胆碱能刺激 脑桥被盖（PbN），单次微量注射卡巴胆碱 产生两相响应：I相由同侧 桥膝枕（PGO）波持续24小时， 影响快速眼动睡眠的模式和数量;第二阶段包括 快速眼动睡眠期的延迟增加，导致300%的 增加每天的快速眼动睡眠总量，并保持这一快速眼动百分比 6-10天内明显升高。 本建议描述了我们计划采取的几种方式， 这个惊人的发现。 首先，我们将绘制和描述放电 PGO/长时程REM增强区细胞的特性，并分析 清醒和清醒状态下PbN/PGO爆发和紧张性神经元与眼运动的关系 在卡巴胆碱激活PbN之前和期间的REM中， 确定两种状态下的时序关系。 第二，我们将使用其他 胆碱能激动剂和拮抗剂药物，以确定 这一限制性区域的神经药理学反应， PGO波触发和长期REM增强。 第三，我们将建立- 加强PGO/长时REM的神经化学特性和连通性 在PbN区的增强区与短潜伏期REM诱导 在旁正中网状结构（PRF）的网站，以确定他们是否是 相互的

Investigation of the triggering mechanism for rapid eye movement (REM) sleep indicates that this behavioral state is produced by the activation of a distributed neuronal network in the paramedian pontine brain stem which leads to the subsequent recruitment of many other neuronal populations throughout the brain. Using single-cell recording, neuronal connectivity mapping, and microinjection pharmacology techniques, considerable progress in delineating the triggering neuronal circuitry of REM sleep has been made but its long term regulation and functional consequences remain obscure. We have recently discovered that exogenous cholinergic stimulation of the endogenous cholinergic peribrachial pontine tegmentum (PbN) with a single microinjection of carbachol produces a two phase response: phase I consists of ipsilateral ponto-geniculo-occipital (PGO) waves which persist for 24 hrs without affecting the pattern and amount of REM sleep; phase II consists of a delayed increase in the number of REM sleep periods that causes a 300% increase in the total amount of REM sleep per day and keeps this REM% significantly elevated for 6-10 days. This proposal describes the several ways in which we plan to follow up on this surprising discovery. First, we will map and characterize discharge properties of cells in the PGO/long-term REM enhancement zone and analyze PbN/PGO burst and tonic neurons in relation to eye movement in waking and in REM both before and during carbachol activation of the PbN to determine the timing relations in both states. Second, we will use other cholinergic agonist and antagonist drugs to determine the neuropharmacological responsiveness of this restricted region in terms of PGO wave triggering and long-term REM enhancement. Third, we will estab- lish the neurochemical identity and connectivity of the PGO/long-term REM enhancement zone in the PbN region with the short-latency REM induction site in the paramedian reticular formation (PRF) to determine if they are reciprocal.