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）：有一个共识，即由于pontis Oralis核（NPO）附近和/或内部和/或内部和/或之内的高管主动睡眠神经元的排放而发生了主动睡眠。这些神经元包括主动睡眠发生器（AS-GENERATOR）。同样普遍认为，As-Generator是通过后dos和Pedunculopontine Nuclei（LDT/PPT）的兴奋性胆碱能投影激活的。但是，各种数据表明，其他站点也可以通过激活ASENERATOR来直接诱导主动睡眠。尚未研究这些位点的直接电生理和神经递质碱基，用于控制AS-Generator的活动睡眠神经元，尚未研究LDT/PPT与ASENERETOR激活来源之间的相互作用。该提案中描述的研究旨在确定概念的真实性，即除了来自LDT/PPT的输入外，位于其他位点的神经元（例如杏仁核的中央核）还能够直接激活AS-ENERERATOR。因此，我们假设He杏仁核和LDT/PPT的中央核不仅独立起作用，而且还可以协同工作，以控制活跃睡眠的滋补和音阶期的发作，持续时间，终止和特征。在先前的假设和我们的初步研究的指导下，我们打算检查NPO中NPO中膜特性的控制，突触机制和分泌模式的神经元中的神经元中的神经元中的神经元中的神经元中心中的中央核中心核中心核中心核。我们还将研究杏仁核中央核中神经元的假定谷氨酸能透射与LDT/PPT启动和维持活跃睡眠的胆碱能投影相互作用。在慢性体内豚鼠制剂中，在自发发生的睡眠和清醒状态以及药物诱发的活性睡眠期间，将采用多学科方法，以互补的技术，程序和神经生物学制剂的使用来采用多学科方法。获得的数据和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基础。我们认为，这些数据也将直接转化为用于治疗主动睡眠疾病的理性疗法，包括REM行为障碍，麻醉症/脱发/瘫痪和不安的腿综合征。这些知识还将为转化研究的全面方法提供关键基础，以治疗涉及杏仁核功能的多种病理，尤其是与情绪和情绪障碍有关的病理，例如抑郁症和PTSD，也涉及干扰主动睡眠的控制。