SYNAPTIC BASIS OF SLEEP CYCLE CONTROL

睡眠周期控制的突触基础

• 批准号: 3486712
• 负责人: Robert W McCarley
• 金额: $ 25.45万
• 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/3486712
• 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.

了解对于控制重要的脑干机制 睡眠的去同步阶段（D），我们将调查 脑桥网状结构 (RF) 的生理学和解剖学 与睡眠相关的核心，以及连通性和 Ch5（桥脚）和 Ch6（背侧）的生理学 胆碱能神经元，因为它们与睡眠有关并与 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 观察到电位（MP）去极化和兴奋性增加 在脑桥内侧网状结构 (mPRF) 群体中 神经元和其他密集连接的射频神经元，并且 胆碱能输入对于引发这些事件可能很重要。 自然条件下的慢性细胞内记录实验 睡觉的猫会检查 mPRF 是否为网状 与网状脊髓神经元相比，投射神经元具有 MP 去极化的较早 D 预期开始，因此 意味着 RF 细胞功能的功能分化和 这些神经元在状态相关变化中发挥特殊作用。 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的时间进程为 放电活动与 D- 的起始相容 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形态 和负责连接的神经元的组织化学性质 脑桥延髓 RF (PBRF) 内、PBRF 与 Ch 5-6 之间，以及 PBRF 的头侧和脊髓投影。 细胞外 和细胞内 HRP 注射技术相结合 将使用 ChAT/AChE 染色。 使用桥脑 RF 切片中的 mPRF 细胞内记录， 我们开发的新型体外制剂，我们建议 来：执行初步识别和表征 mPRF-mPRF 神经递质；识别固有电压- 依赖电流对于 D 状态相关的调节很重要 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。