Neural circuitry in stress-induced insomnia

压力引起的失眠的神经回路

• 批准号: 6957295
• 负责人: GEORGINA CANO
• 金额: $ 2.33万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6957295
• 关键词: afferent nerve; apoptosis; behavioral /social science research tag; brain electrical activity; catecholamines; fos protein; galanin; gamma aminobutyrate; gene expression; immunocytochemistry; in situ hybridization; laboratory rat; neural transmission; neuroanatomy; orexin; phenotype; postdoctoral investigator; preoptic areas; psychic activity level; psychological stressor; psychosomatic disorders; serotonin; sleep; sleep disorders; wakefulness

DESCRIPTION (provided by candidate): Primary insomnia is the most prevalent sleep disorder in the general population. Stressful life events have been proposed as major factors since insomniacs show alterations in stress hormone levels and, conversely, experimental insomnia can be induced by stress neuropeptides. Nevertheless, little is known about the central pathways underlying the effects of stress on the sleep-wake cycle. Activation of the ventrolateral preoptic nucleus (VLPO) is necessary to produce normal sleep, whereas during wakefulness the VLPO is strongly inhibited by inputs from wake-promoting areas. It has been proposed that the stability of the sleep-wake cycle depends on reciprocal inhibitory interactions between the VLPO and wake-promoting areas. Alterations of sleep architecture, such as those observed in insomnia, most likely involve changes in the neuronal activity of the sleep-wake circuitry. Animal models may be very useful to study the anatomical and functional relation between stress and sleep-wake circuits during insomnia. We propose to use acute exposure to a psychological stressor that causes transient insomnia as a simple model to study the basic functional changes elicited by stress on the sleep-wake circuitry. Our hypothesis is that insomnia is caused by decreased VLPO activity evoked by activation of specific inhibitory VLPO afferents that are stress-sensitive. The aims of this proposal are to determine whether: (1) specific VLPO afferents are activated during stress-induced insomnia, (2) they provide inhibitory inputs to VLPO, and (3), selective destruction of these afferents attenuates transient insomnia. Understanding the biological mechanisms underlying stress-induced transient insomnia will provide an essential framework for future studies of chronic insomnia and will help to identify targets for more specific pharmacological treatments.

描述（由候选人提供）：主要失眠是普通人群中最普遍的睡眠障碍。由于失眠症显示压力激素水平的改变，因此已经提出了应力生命事件，这是主要因素，相反，可以通过压力神经肽诱导实验性失眠。然而，关于压力对睡眠效果周期影响的基础的中心途径知之甚少。腹外侧前核（VLPO）的激活对于产生正常睡眠是必要的，而在唤醒期间，VLPO受到启动唤醒区域的输入的强烈抑制。已经提出，睡眠效果周期的稳定性取决于VLPO和启动唤醒区域之间的相互抑制作用。睡眠结构的改变，例如在失眠症中观察到的改变，很可能涉及睡眠觉醒电路神经元活动的变化。动物模型对于研究失眠期间的压力和睡眠效果回路之间的解剖和功能关系可能非常有用。我们建议使用急性暴露于心理压力源，该心理压力源会导致短暂失眠作为一个简单模型，以研究通过压力在睡眠效果电路上引起的基本功能变化。我们的假设是失眠是由于激活应激敏感的特定抑制性VLPO传入所引起的VLPO活性降低引起的。该提案的目的是确定：（1）在压力引起的失眠期间激活特定的VLPO传入，（2）它们向VLPO提供抑制投入，（3），这些传入的选择性破坏会减弱短暂的失眠症。了解应激引起的瞬时失眠的生物学机制将为将来的慢性失眠研究提供一个重要的框架，并将有助于确定更具体的药理治疗目标。