Limbic modulation of stress-induced alterations in sleep

描述(由申请者提供)：我们研究项目的长期目标是了解压力事件对睡眠的影响，进而了解睡眠变化与压力持续影响的关系。压力源和条件性/习得性的压力源提醒会在行为和睡眠方面产生重大变化。这些变化可能随应激源的强度和可控性以及是否制定了成功的应对策略而有所不同。在神经生物学水平上，这种改变可能涉及到与压力和情绪有关的边缘区域的CRH，以及对觉醒的控制。然而，应激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，目前还知之甚少。在这个项目中，我们打算确定应激源强度和可控性的变化如何影响应激后睡眠，我们打算确定杏仁核中CRH及其相关神经肽在调节觉醒和应激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制是否与与应激有关的脑区和与睡眠和应激调节有关的脑干单胺能细胞群的活动变化有关。为了完成这项应用的目标，我们将：1)确定应激源强度和可控性在应激对睡眠和行为影响中的作用(S)，2)确定杏仁核CRH1和CRH2受体在调节唤醒和睡眠方面的作用(S)，3)确定杏仁核CRH1和CRH2受体在应激诱导的唤醒和睡眠改变中的作用(S)，4)我们将确定与应激有关的区域和在应激诱导的快速眼动睡眠改变中的区域，这是可能受应激影响最大的睡眠状态。我们还将测量心率和呼吸频率以及应激反应的血浆标记物。了解可控和不可控压力引起睡眠变化的神经生物学基础将增加我们对压力和应激相关情绪如何影响睡眠的理解，进而了解睡眠改变在应激相关病理发展中可能发挥的作用。这样的理解可能会提供对失眠等睡眠障碍的洞察，以及对影响睡眠的情绪障碍的洞察。这对于深入了解创伤后应激障碍(PTSD)尤其相关，创伤后应激障碍的特征是在心理创伤应激源后睡眠障碍。公共卫生相关性这项研究的目标是了解压力事件对睡眠的影响，进而了解睡眠变化与压力持续影响的关系。压力源，甚至是对压力源的条件性提醒，都会在行为和睡眠方面产生重大变化。众所周知，应激源强度和可控性的影响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是如何影响睡眠的，也不知道睡眠改变在压力的长期影响中可能起到什么作用。我们将确定应激源强度和可控性如何影响应激后睡眠，并将研究杏仁核中促肾上腺皮质激素释放激素在调节应激后睡眠中的作用。杏仁核是大脑中的情绪中心。这些研究提供的洞察力可能会改善失眠等睡眠障碍的治疗，以及影响睡眠的情绪障碍的治疗。这对于理解和治疗创伤后应激障碍(PTSD)特别相关，创伤后应激障碍(PTSD)的特征是在心理创伤应激后睡眠障碍。

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.