SYNAPTIC BASIS OF SLEEP CYCLE CONTROL

睡眠周期控制的突触基础

• 批准号: 2244817
• 负责人: Robert W McCarley
• 金额: $ 27.01万
• 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 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2244817
• 关键词: REM sleep; antidromic impulse; behavior test; brain electrical activity; brain mapping; cats; circadian rhythms; dorsal raphe nucleus; electroencephalography; electromyography; electrooculography; histology; locus coeruleus; membrane potentials; neural inhibition; pons; reticular formation; sleep; sleep regulatory center

To understand brain stem mechanisms important for control of the desynchronized phase of sleep (D), we shall investigate the physiology and anatomy of the pontine reticular formation (RF) core as related to sleep, and aspects of connectivity and physiology of the Ch5 (pedunculopontine) and Ch6 (laterodorsal) cholinergic neurons as they relate to sleep and connections with pontobulbar reticular formation. A guiding hypothesis is that an essential element of the occurrence of D is the membrane potential (MP) depolarization and increased excitability observed in the population of medial pontine reticular formation (mPRF) neurons and other, densely connected RF neurons, and that cholinergic input may be important for initiating these events. Chronic intracellular recording experiments in the naturally sleeping cat will examine whether mPRF reticulo-reticular projection neurons have, compared with reticulo-spinal neurons, an earlier, D-anticipatory onset of MP depolarization, thus implying functional differentiation of RF cellular function and a special role in state-related changes for these neurons. Chronic intracellular and extracellular recordings will determine if cholinergic neurons in the Ch5-Ch6 groups have a time course of discharge activity that is compatible with initiation of D- anticipatory events in mPRF. Intracellular HRP combined with acetylcholinesterase (AChE) or choline acetyltransferase (ChAT) labeling will identify recorded neurons. Anatomical- physiological studies in acute cats will examine the morphology and histochemical nature of neurons responsible for connectivity within pontobulbar RF (PBRF), between PBRF and Ch 5-6, and the rostral and spinal cord projections of PBRF. Extracellular and intracellular HRP injection techniques combined with ChAT/AChE staining will be used. Using mPRF intracellular recordings in the pontine RF slice, a novel in vitro preparation developed by us, we propose to: perform initial identification and characterization of the mPRF-mPRF neurotransmitter(s); identify intrinsic voltage- dependent currents important for mediation of D state-related changes; and characterize the effects of cholinergic agonists. Better understanding of D mechanisms will aid development of more rational treatment of disorders with D sleep pathology, including depression and narcolepsy.

了解脑干机制对于控制 睡眠的干燥阶段（D），我们将调查 庞蒂定性形成（RF）的生理学和解剖学 与睡眠有关的核心以及连通性的各个方面 CH5（Pedunculopontine）和CH6的生理学（LaterodorSal） 胆碱能神经元与睡眠和连接有关 pontobulbar网状形成。 指导假设是 D发生的基本要素是膜 电势（MP）去极化和观察到的兴奋性增加 在内侧庞蒂定形成（MPRF）中 神经元和其他连接的RF神经元，并且 胆碱能输入对于启动这些事件可能很重要。 自然中的慢性细胞内记录实验 熟睡的猫会检查MPRF是否续线 与网状神经元相比，投射神经元具有 MP去极化的较早的D-审判性发作，因此 暗示RF细胞功能的功能分化和A 这些神经元与国家相关的变化中的特殊作用。 慢性的 细胞内和细胞外记录将确定是否 CH5-CH6组中的胆碱能神经元有一个时间课程 与D-兼容的排放活性 MPRF中的预期事件。 细胞内HRP与 乙酰胆碱酯酶（ACHE）或胆碱乙酰转移酶（CHAT） 标签将识别记录的神经元。 解剖学 急性猫的生理研究将检查形态 以及负责连通性的神经元的组织化学性质 在Pontobulbar RF（PBRF）中，PBRF和CH 5-6之间，以及 PBRF的脊髓和脊髓投影。 细胞外 和细胞内HRP注射技术与 将使用聊天/疼痛染色。 在蓬托RF切片中使用MPRF细胞内记录 我们开发的新型体外准备，我们提出 到：执行初始识别和表征 MPRF-MPRF神经递质（S）;识别固有电压 - 依赖电流对于调解D状态有关 变化；并表征胆碱能激动剂的作用。 更好地了解D机制将有助于发展 对患有D睡眠病理的疾病的更多理性治疗， 包括抑郁症和发作性睡病。