THE SYNAPTIC BASIS OF SLEEP CYCLE CONTROL

睡眠周期控制的突触基础

• 批准号: 3377604
• 负责人: Robert W McCarley
• 金额: $ 13.19万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3377604
• 关键词: REM sleep; antidromic impulse; behavior test; brain electrical activity; brain mapping; circadian rhythms; dorsal raphe nucleus; electroencephalography; electromyography; electrooculography; histology; membrane potentials; sleep

To discover the synaptic mechanisms operating during the sleep cycle and responsible for control of various aspects of the rapid eye movement (REM) or desynchronized (D) phase of sleep, I propose to do intracellular recordings in medial pontine reticular formation (mPRF) neurons during naturally occurring sleep-waking cycles in unanesthetized, undrugged cats. Physiological identification and characterization of neurons will be made by correlation of the intracellular recordings with both electrographic data of the sleep cycle (i.e., EEG, EMG, EOG records) and with the effects of microstimulation-induced post-synaptic potentials and antidromic activation from sites located in the mesencephalic, bulbar and contralateral pontine reticular formation and in the locus coerulus and dorsal raphe nucleus. Identification of morphological characteristics of neurons associated with particular physiological properties will be made through HRP injections into neurons intracellularly recorded in the naturally sleeping cat. These studies will address several questions of fundamental importance to knowledge of how the brain controls its excitability during the sleep-wake cycle: Are there D-specific changes in the mPRF suggestive of an involvement of this region in generation of some D phenomena and perhaps of initiation of the state itself, and, if so, what are the mechanisms of these changes? Do our initial findings of D-specific changes of tonic membrane depolarization, decreased membrane input resistance, and increased excitability apply to all cell types and areas in PRF? Is one mechanism for these alterations disinhibition by biogenic-amine containing cells in the locus coeruleus and dorsal raphe? Does a recently discovered dorso-rostral zone of inhibitory input to mPRF neurons play an important role in PGO wave generation and other D phenomena? Do cells in the most medial portion of mPRF initiate PGO waves? Answers to these questions have broad implications for psychiatry, where knowledge of mechanisms of brain state regulation is basic for this field, but where there are few studies in naturally behaving vertebrates. The now well-known correlation between D sleep abnormalities and endogeneous depression suggests a specific link between aspects of pysiological control mechanisms important in affective disorder and in D. These studies are also relevant to the study of sleep disorders, especially narcolepsy, and to the use in psychiatry of the dream state as a model for psychosis.

为了发现在睡眠周期中运作的突触机制 负责控制眼球快速运动(REM)的各个方面 或睡眠的去同步化(D)阶段，我建议做细胞内 脑桥内侧网状结构(MPRF)神经元的记录 未麻醉、未下药的猫自然出现的睡眠-觉醒周期。 将对神经元进行生理学鉴定和特征描述 通过将细胞内记录与两种脑电记录相关联 睡眠周期的数据(即EEG、EMG、EOG记录)及其影响 微刺激诱导的突触后电位与逆行反应 来自中脑、延髓和中脑的激活 对侧脑桥网状结构和蓝斑和 中缝背核。冬虫夏草形态特征的鉴定 与特定生理特性相关的神经元将被制造出来 通过将HRP注射到细胞内记录的神经元中 自然入睡的猫。这些研究将解决以下几个问题 对了解大脑如何控制大脑的基本重要性 睡眠-觉醒周期中的兴奋性：在睡眠-觉醒周期中是否有D特有的变化 Mprf暗示这一区域参与了一些 D现象，也许是国家本身的启动，如果是的话，是什么 这些变化的机制是什么？我们最初发现的特定于D的 紧张膜去极化改变，膜输入减少 抵抗力和兴奋性增加适用于所有细胞类型和区域 PRF？是这些改变解除抑制的一种机制，通过 蓝斑和中缝背侧含有生物胺的细胞？ 最近发现的抑制mPRF输入的背喙区 神经元在PGO波和其他D波的产生中起重要作用 现象？MPRF最内侧的细胞启动PGO吗 海浪？这些问题的答案对精神病学有着广泛的影响， 其中对大脑状态调节机制的了解是实现这一点的基础 但在那里对自然行为的脊椎动物的研究很少。 众所周知，D睡眠异常和睡眠障碍之间的关联 内源性抑郁提示在以下几个方面之间存在特定联系 在情感性精神障碍和D。 这些研究也与睡眠障碍的研究有关，特别是 发作性睡病，以及在精神病学中将梦状态作为 精神错乱。