NEUROPHYSIOLOGICAL MECHANISMS OF SLEEP CYCLE CONTROL

快速眼动(REM)的触发机制研究 睡眠表示这种行为状态是由激活产生的 桥旁正中脑干的分布神经元网络 这导致了随后许多其他神经元的招募 整个大脑中的种群。使用单细胞记录，神经元 连接性测绘和微注射药理学技术， 在描绘触发神经回路方面取得了相当大的进展 REM睡眠已经完成，但它的长期调节和功能 后果仍不明朗。我们最近发现，外源的 内源性胆碱能臂周围区的胆碱能刺激 单次微量注射卡巴胆碱桥脑被盖(PBN) 产生两个阶段的反应：阶段I由同侧 持续24小时的脑桥-膝枕(PGO)波 影响快速眼动睡眠的模式和时间；第二阶段包括 REM睡眠周期的延迟增加导致300% 增加每天的快速眼动睡眠总量，并保持这一速度百分比 在6-10天内显著升高。 这项建议描述了我们计划采取后续行动的几种方式 这个令人惊讶的发现。首先，我们将绘制和表征放电 PGO/长期REM增强区细胞的特性及分析 觉醒与眼球运动相关的PBN/PGO爆发性神经元和紧张性神经元 在激活PBN之前和期间的REM中 确定两个状态下的时序关系。第二，我们将使用其他 胆碱能激动剂和拮抗剂药物测定 这一受限区域的神经药理学反应性 PGO波触发和长期REM增强。第三，我们将建立- 了解PGO/Long-Term REM的神经化学特性和连接性 短潜伏期REM诱发的PBN区增强区 旁正中网状结构(PRF)的位置，以确定它们是否 互惠。

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.