The Control of Active (REM) Sleep by the Amygdala

杏仁核对活跃 (REM) 睡眠的控制

• 批准号: 7354134
• 负责人: MICHAEL H CHASE
• 金额: $ 40.58万
• 依托单位: WEBSCIENCES INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-15 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7354134
• 关键词: Affect; Amygdaloid structure; Animals; Anxiety; Behavior; Belief; Brain Stem; Cataplexy; Cavia; Cell Nucleus; Characteristics; Cholinergic Agents; Cholinergic Agonists; Cholinergic Antagonists; Chronic; Clinical; Consensus; Data; Development; Disease; Disruption; Emotional; Emotions; Foundations; Generations; Glutamates; Human; Knowledge; Link; Mediating; Medicine; Membrane; Mental Depression; Mental disorders; Microdialysis; Mood Disorders; Moods; Morphology; Narcolepsy; Neurobiology; Neurons; Neurotransmitters; Pathology; Pattern; Phenotype; Play; Pontine structure; Post-Traumatic Stress Disorders; Preparation; Procedures; Process; Property; Prosencephalon; REM Sleep; REM Sleep Behavior Disorder; Research; Restless Legs Syndrome; Role; Series; Site; Sleep; Sleep Disorders; Source; Stress; Synapses; System; Techniques; Testing; Translating; Translational Research; Wakefulness; Work; base; cholinergic; concept; design; disturbance in affect; emotional factor; emotional stimulus; improved; in vivo; insight; interdisciplinary approach; multidisciplinary; neuromechanism; research study; sleep regulation; transmission process

DESCRIPTION (provided by applicant): There is a consensus that active (REM) sleep occurs as a result of the discharge of executive active sleep-on neurons that are located in and/or within the vicinity of the nucleus pontis oralis (NPO); these neurons comprise the active sleep generator (AS-Generator). It is also universally accepted that the AS-Generator is activated by excitatory cholinergic projections from the laterodorsal and pedunculopontine nuclei (LDT/PPT). However, a variety of data suggest that other sites may also be capable of directly inducing active sleep by activating the AS-Generator. The direct electrophysiological and neurotransmitter bases for the control of active sleep-on neurons of the AS-Generator by these sites has not been examined, nor have interactions between the LDT/PPT and other sources of activation of the AS-Generator been explored. The research described in the proposal is designed to determine the veracity of the concept that, in addition to input from the LDT/PPT, neurons that are located in other sites, such as the central nucleus of the amygdala, are capable of directly activating the AS-Generator. Thus, we hypothesize that the central nucleus of he amygdala and the LDT/PPT not only function independently, but also work cooperatively, to control the onset, duration, termination and characteristics of the tonic and phasic periods of active sleep. Guided by the preceeding hypotheses and our Preliminary Studies, we intend to examine the control of the membrane properties, synaptic mechanisms and patterns of discharge of AS-Generator neurons in the NPO by neurons in the central nucleus of the amygdala. We will also examine the manner in which putative glutamatergic projections from neurons in the central nucleus of the amygdala interact with cholinergic projections from the LDT/PPT in initiating and maintaining active sleep. A multidisciplinary approach will be employed based upon the use of complementary techniques, procedures and neurobiological preparations in the chronic in vivo guinea pig preparation during spontaneously occurring states of sleep and wakefulness as well as during pharmalogically-induced active sleep. The data that are obtained and the verification of our hypotheses will provide important foundational bases for understanding the sites and neuronal mechanisms that control active sleep. We believe that these data will also be directly translatable to the development of rational therapies for the treatment of disorders of active sleep including REM Behavior Disorder, narcolepsy/cataplexy, and Restless Legs Syndrome. This knowledge will also provide a key foundation for a comprehensive approach to translational research to treat diverse pathologies that involve amygdala functions, especially those related to emotion and mood disorders, such as depression and PTSD, that also involve disruptions in the control of active sleep.

描述（由申请人提供）：人们一致认为，主动（REM）睡眠是由于位于口桥核（NPO）内和/或附近的执行主动睡眠神经元放电而发生的；这些神经元组成了主动睡眠发生器（AS-Generator）。人们还普遍认为 AS 发生器是由背外侧核和桥脚核 (LDT/PPT) 的兴奋性胆碱能投射激活的。然而，各种数据表明其他位点也可能能够通过激活 AS 生成器直接诱导主动睡眠。尚未检查这些位点用于控制 AS 生成器的活跃睡眠神经元的直接电生理学和神经递质基础，也没有探索 LDT/PPT 与 AS 生成器的其他激活源之间的相互作用。该提案中描述的研究旨在确定这一概念的准确性，即除了来自 LDT/PPT 的输入之外，位于其他部位（例如杏仁核中央核）的神经元也能够直接激活 AS 生成器。因此，我们假设杏仁核中央核和LDT/PPT不仅独立发挥作用，而且协同工作，控制主动睡眠的强直期和阶段性周期的开始、持续时间、终止和特征。在前述假设和我们的初步研究的指导下，我们打算检查杏仁核中央核神经元对 NPO 中 AS 生成器神经元的膜特性、突触机制和放电模式的控制。我们还将研究杏仁核中央核神经元的假定谷氨酸能投射与 LDT/PPT 的胆碱能投射在启动和维持活跃睡眠中相互作用的方式。将采用多学科方法，基于在自发发生的睡眠和觉醒状态以及药物诱导的主动睡眠期间慢性体内豚鼠准备中使用补充技术、程序和神经生物学制剂。获得的数据和对我们假设的验证将为理解控制主动睡眠的部位和神经元机制提供重要的基础基础。我们相信，这些数据也将直接转化为治疗主动睡眠障碍的合理疗法的开发，包括快速眼动行为障碍、发作性睡病/猝倒症和不宁腿综合症。这些知识还将为转化研究的综合方法提供关键基础，以治疗涉及杏仁核功能的各种病理学，特别是与情绪和心境障碍相关的病理学，例如抑郁症和创伤后应激障碍（PTSD），这些疾病也涉及主动睡眠控制的破坏。