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）：一致认为主动（REM）睡眠是位于脑桥口核（NPO）中和/或其附近的执行性主动睡眠神经元放电的结果;这些神经元包括主动睡眠发生器（AS-发生器）。也普遍认为AS发生器是由来自背外侧核和脚桥核（LDT/PPT）的兴奋性胆碱能投射激活的。然而，各种数据表明，其他部位也可能能够通过激活AS发生器直接诱导主动睡眠。这些位点控制AS-发生器的活跃睡眠神经元的直接电生理学和神经递质基础尚未研究，LDT/PPT与AS-发生器激活的其他来源之间的相互作用也未进行探索。该提案中描述的研究旨在确定以下概念的准确性：除了来自LDT/PPT的输入之外，位于其他部位的神经元，例如杏仁核的中央核，能够直接激活AS发生器。因此，我们推测杏仁中央核和LDT/PPT不仅独立地发挥作用，而且还协同工作，以控制主动睡眠的紧张期和相位期的开始、持续时间、终止和特征。在上述假设和我们的初步研究的指导下，我们打算研究杏仁中央核神经元对NPO中AS-发生器神经元的膜特性、突触机制和放电模式的控制。我们还将研究在启动和维持主动睡眠中，杏仁核中央核中神经元的推定神经元投射与LDT/PPT的胆碱能投射相互作用的方式。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，在慢性体内豚鼠制备中使用补充技术、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了解控制主动睡眠的位点和神经元机制提供重要的基础。我们相信，这些数据也将直接转化为治疗活跃睡眠障碍的合理疗法的发展，包括REM行为障碍，嗜睡症/癫痫和不宁腿综合征。这些知识也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，特别是与情绪和心境障碍有关的疾病，如抑郁症和创伤后应激障碍，这些疾病也涉及主动睡眠控制的中断。