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: 8631202
• 负责人: LARRY D SANFORD
• 金额: $ 36.63万
• 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 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8631202
• 关键词: Affect; Agonist; Amygdaloid structure; Anxiety Disorders; Arousal; Behavior; Behavioral; Biosensing Techniques; Biosensor; Brain region; Calcium; Calmodulin; Cell Nucleus; Chloride Ion; Chlorides; Corticotropin-Releasing Hormone; Data; Development; Disease; Dissociation; Elements; Emotional; Emotional disorder; Event; Excitatory Amino Acid Antagonists; Extinction (Psychology); Freezing; Fright; Glutamate Agonist; Glutamates; Grant; Induced Hyperthermia; Intervention; Ions; Knowledge; Learning; Light; Link; Measures; Mediating; Memory; Mental disorders; Modeling; Mood Disorders; Mus; Muscimol; Neurobiology; Neurons; Opsin; Oxidases; Phosphotransferases; Physiological; Play; Process; REM Sleep; Regulation; Relative (related person); Research; Rodent; Role; Sleep; Sleep disturbances; Sodium; Stimulus; Stress; System; Testing; Time; Wakefulness; Work; base; biological adaptation to stress; cellular transduction; clinically relevant; conditioned fear; conditioning; experience; expression vector; extracellular; improved; insight; neural circuit; neurobiological mechanism; neuromechanism; optogenetics; prevent; promoter; public health relevance; rapid eye movement; research study; response

Project Summary/Abstract Problems with fear memory and fear extinction (new learning that reduces fear) are core elements of a variety of psychiatric disorders. Fear-related learning is thought to play a significant role in the development of emotional disorders and fear conditioning (usually employing footshock as the fear-inducing stimulus) is a key research model used in this work. After conditioning, memories of the fearful experience produce virtually identical behavioral and physiological responses to those elicited by footshock. Fear also has a significant impact on sleep. One prominent effect of fear on sleep is reduced rapid eye movement (REM) sleep that occurs in the period after certain fearful experiences. However, fear behavior and subsequent sleep can dissociate depending on the conditions in which fear occurs. Fear learning associated with uncontrollable stress produces overt fear behavior in wakefulness (freezing in rodents) and decreases REM sleep whereas fear learning associated with controllable stress produces similar fear behavior in wakefulness but can increase REM sleep. Sleep disturbances occur in essentially all psychiatric disorders; therefore, understanding the neurobiological processes by which stressful and fearful events can alter the impact of emotional memory on sleep can provide insight needed to improve treatments in disorders in which sleep is impacted. We recently found that the basolateral amygdala (BLA) plays a critical role in determining whether fear memory alters sleep. In this project, we will establish the role of BLA in mediating the impact of fear on sleep by determining its role in fear learning, fear memory consolidation and fear extinction. We will determine the effects of global inactivation of BLA on sleep, fear behavior and the stress response during fear learning, fear memory consolidation and fear extinction. We will determine how clinically relevant systems (i.e., corticotropin releasing factor and metabotropic glutamate) alter fear learning, fear memory consolidation and fear extinction, and their effects on sleep, fear behavior and the stress response. We will use biosensors to assess in near real time how glutamate changes in BLA in association with fear learning, fear memory consolidation and fear extinction and with spontaneous changes in arousal state. Lastly, we will use optogenetics to activate and inhibit glutamate neurons in BLA to delineate which specific fear processes (fear learning, fear memory and fear extinction) the BLA regulates. These studies will fill in a significant knowledge gap by increasing our understanding of the association between fear, sleep, and stress, and the neurobiological processes by which fearful memories come to affect sleep.

项目总结/文摘