Limbic modulation of stress-induced alterations in sleep

压力引起的睡眠改变的边缘调节

• 批准号: 8259805
• 负责人: LARRY D SANFORD
• 金额: $ 31.96万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2013-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8259805
• 关键词: Affect; Amygdaloid structure; Argipressin; Arousal; Behavior; Behavioral; Biological Assay; Brain; Brain Stem; Brain region; Cells; Characteristics; Corticosterone; Corticotropin; Corticotropin-Releasing Hormone; Cues; Development; Electroencephalography; Emotional; Emotional disorder; Emotions; Epinephrine; Event; Fright; Goals; Health; Heart; Label; Lead; Learning; Link; Long-Term Effects; Measures; Modeling; Neurobiology; Neuropeptides; Norepinephrine; Nucleic Acid Regulatory Sequences; Organism; Outcome; Pathology; Peptides; Peripheral; Plasma; Play; Post-Traumatic Stress Disorders; Prolactin; REM Sleep; Recovery; Regulation; Research; Role; Serotonin; Shock; Sleep; Sleep Disorders; Sleeplessness; Stimulus; Stress; Stressful Event; System; Training; Tyrosine 3-Monooxygenase; Variant; Work; base; biological adaptation to stress; conditioned fear; coping; dorsal raphe nucleus; improved; insight; locus ceruleus structure; paraventricular nucleus; programs; receptor; relating to nervous system; resilience; respiratory; sleep regulation; stressor

DESCRIPTION (provided by applicant): The long-term goal of our research program is to understand the impact of stressful events on sleep, and, in turn, how alterations in sleep are related to the persisting effects of stress. Stressors and conditioned/learned reminders of stressors can produce significant alterations in behavior and sleep. These alterations may vary with the intensity and controllability of the stressor and whether a successful coping strategy was developed. At the neurobiological level, the alterations may involve CRH in limbic regions implicated in stress and emotion, and in the control of arousal. However, the relationship between stress-induced behaviors and alterations in sleep, and their behavioral and neurobiological bases, are poorly understood. In this project, we intend to determine how variations in stressor intensity and controllability can influence post-stress sleep, and we intend to determine the role of CRH and CRH-related neuropeptides in the amygdala in regulating arousal and stress- induced alterations in sleep. Lastly, we will determine whether amygdalar modulation of stress-induced changes in arousal is associated with alterations in activity in brain regions implicated in stress and in brainstem monoaminergic cell groups that have been linked to the regulation of sleep and stress. To accomplish the objectives of this application we will: 1) determine the role(s) of stressor intensity and controllability in the effects of stress on sleep and behavior, 2) determine the role(s) of CRH1 and CRH2 receptors in the amygdala in regulating arousal and sleep, 3) determine the role(s) of CRH1 and CRH2 receptors in the amygdala in stress-induced alterations in arousal and sleep, and 4) we will identify regions involved in stress and in stress-induced alterations in rapid eye movement sleep, the sleep state that may be most impacted by stress. We will also measure heart and respiratory rate and plasma markers of the stress response. Understanding the neurobiology underlying the changes in sleep induced by controllable and uncontrollable stress should increase our understanding of how stress and stress-related emotion affect sleep and, in turn, the role altered sleep may play in the development of stress-related pathology. Such understanding may provide insight into sleep disorders such as insomnia and into emotional disorders in which sleep is affected. It will be especially relevant for insight into posttraumatic stress disorder (PTSD), which is characterized by disturbed sleep after a psychologically traumatic stressor. PUBLIC HEALTH RELEVANCE The goal or this research is to understand the impact of stressful events on sleep, and, in turn, how alterations in sleep are related to the persisting effects of stress. Stressors and even conditioned reminders of stressors can produce significant alterations in behavior and sleep. It is known that the effects of stressor intensity and controllability are important factors in the long-term effects of stress. However, it is not know how these factors impact sleep, or what role altered sleep may play in the long-term effects of stress. We will determine how stressor intensity and controllability affect post-stress sleep, and we will examine the role of corticotropin releasing hormone in the amygdala, a center of emotion in the brain, in regulating post-stress sleep. The insight provided by these studies may lead to improved treatments for sleep disorders such as insomnia and into emotional disorders in which sleep is affected. It will be especially relevant for understanding and potential treatment of posttraumatic stress disorder (PTSD), which is characterized by disturbed sleep after a psychologically traumatic stressor.

描述（由申请人提供）：我们研究计划的长期目标是了解压力事件对睡眠的影响，以及睡眠的改变如何与压力的持续影响相关。压力源和压力源的条件反射/习得的提醒可以在行为和睡眠方面产生显著的改变。这些变化可能会随着压力源的强度和可控性以及是否制定了成功的应对策略而变化。在神经生物学水平上，这些改变可能涉及与压力和情绪有关的边缘系统区域的CRH，以及对唤醒的控制。然而，压力诱导的行为和睡眠改变之间的关系，以及它们的行为和神经生物学基础，知之甚少。在这个项目中，我们打算确定压力强度和可控性的变化如何影响压力后睡眠，我们打算确定杏仁核中CRH和CRH相关神经肽在调节唤醒和压力诱导的睡眠改变中的作用。最后，我们将确定杏仁核对应激诱导的觉醒变化的调节是否与应激脑区和脑干单胺能细胞群（与睡眠和应激调节有关）的活动改变有关。为了实现本申请的目标，我们将：1）确定应激强度和可控性在应激对睡眠和行为的影响中的作用，2）确定杏仁核中CRH 1和CRH 2受体在调节觉醒和睡眠中的作用，3）确定杏仁核中CRH 1和CRH 2受体在应激诱导的觉醒和睡眠改变中的作用，以及4）我们将确定涉及压力和压力诱导的快速眼动睡眠改变的区域，快速眼动睡眠是可能受压力影响最大的睡眠状态。我们还将测量心率和呼吸率以及应激反应的血浆标志物。了解可控和不可控压力引起的睡眠变化的神经生物学基础，应该增加我们对压力和压力相关情绪如何影响睡眠的理解，反过来，改变睡眠可能在压力相关病理学发展中发挥的作用。这样的理解可以提供对睡眠障碍如失眠和影响睡眠的情绪障碍的洞察。这将是特别相关的洞察创伤后应激障碍（PTSD），这是一个心理创伤压力源后的睡眠障碍的特点。本研究的目的是了解压力事件对睡眠的影响，以及睡眠的改变如何与压力的持续影响相关。压力源，甚至是压力源的条件性提醒，都能导致行为和睡眠的显著改变。众所周知，应激强度和可控性是影响应激长期效应的重要因素。然而，目前还不知道这些因素如何影响睡眠，或者睡眠改变在压力的长期影响中可能发挥什么作用。我们将确定压力强度和可控性如何影响压力后睡眠，我们将检查杏仁核中促肾上腺皮质激素释放激素的作用，大脑中的情绪中心，在调节压力后睡眠。这些研究提供的见解可能会导致改善对睡眠障碍（如失眠）和影响睡眠的情绪障碍的治疗。这将是特别相关的理解和潜在的治疗创伤后应激障碍（PTSD），这是一个心理创伤应激源后的睡眠障碍的特点。