THE SYNAPTIC BASIS OF SLEEP CYCLE CONTROL

睡眠周期控制的突触基础

• 批准号: 3486706
• 负责人: Robert W McCarley
• 金额: $ 25.6万
• 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 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3486706
• 关键词: REM sleep; antidromic impulse; behavior test; brain electrical activity; brain mapping; circadian rhythms; dorsal raphe nucleus; electroencephalography; electromyography; electrooculography; histology; locus coeruleus; membrane potentials; 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.

为了了解脑干机制的重要控制 在睡眠的去睡眠阶段（D），我们将研究 脑桥网状结构（RF）的生理和解剖 与睡眠有关的核心，以及连接和 Ch5（脚桥）和Ch6（侧背）生理学 胆碱能神经元与睡眠有关， 脑桥延髓网状结构 一个指导性假设是， D发生的基本要素是膜 观察到潜在（MP）去极化和兴奋性增加 在脑桥内侧网状结构（mPRF）人群中 神经元和其他密集连接的RF神经元， 胆碱能输入对于启动这些事件可能是重要的。 慢性细胞内记录实验 睡觉的猫将检查mPRF网状-网状 与网状脊髓神经元相比，投射神经元具有， MP去极化的早期、D-预期发作，因此 这意味着RF细胞功能的功能分化， 在这些神经元的状态相关变化中的特殊作用。 慢性 细胞内和细胞外记录将确定 Ch5-Ch6组的胆碱能神经元有一个时间过程， 放电活动与D-启动兼容， mPRF中的预期事件。 细胞内HRP结合 乙酰胆碱酯酶（AChE）或胆碱乙酰转移酶（ChAT） 标记将识别记录的神经元。 解剖学- 急性猫的生理学研究将检查 和负责连接的神经元的组织化学性质 脑桥延髓RF（PBRF）内，PBRF和Ch 5 - 6之间，以及 PBRF的吻侧和脊髓投射。 细胞外 和细胞内HRP注射技术结合 将使用ChAT/AChE染色。 使用脑桥RF切片中的mPRF细胞内记录， 我们开发了一种新的体外制剂，我们建议 进行初步鉴定和定性 mPRF-mPRF神经递质;确定固有电压- 依赖电流对于D状态相关的介导很重要 变化;并表征胆碱能激动剂的作用。 更好地理解D机制将有助于开发 更合理地治疗D睡眠病理障碍， 包括抑郁症和嗜睡症