AMYGDALAR MODULATION OF BRAINSTEM ALERTING MECHANISMS

脑干警报机制的杏仁核调节

• 批准号: 2431311
• 负责人: LARRY D SANFORD
• 金额: $ 11.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2431311
• 关键词: REM sleep; alpha adrenergic receptor; amygdala; arousal; auditory stimulus; brain stem; corticotropin releasing factor; electroencephalography; electromyography; electrophysiology; electrostimulus; fear; inhibitor /antagonist; laboratory rat; medial geniculate body; microinjections; neuropharmacology; neurophysiology; neuropsychology; norepinephrine; occipital lobe /cortex; serotonin; startle reaction; wakefulness

Brain activity during rapid eye movement sleep (REM) resembles that of a state of hyperalertness, with electrophysiological features also found in alert waking (EEG activation, hippocampal theta and PGO wave activity). There is good evidence that the pinto-genicula-occipital (PGO) wave, a defining feature of REM, and its sound-elicited analog (PGO-epsilon) are neural indicators of alerting. Paradoxically, during REM, brain mechanisms of alerting are endogenously activated at the same time that largely unknown mechanisms prevent translation of that brain activity into behavioral arousal. The amygdala may have a role in modulating arousal and the generation of many of the features common to alert waking and REM. The central nucleus of the amygdala (CNA) projects prominently directly into brainstem regions important in the generation of REM and PGO waves. Thus, CNA provides a pathway by which the limbic system may influence alerting mechanisms and behavioral state; and it may be that this influence could be a significant factor in REM induction and maintenance. This project will examine CNA modulation of arousal and alerting in albino rats using standard indices (EEO, EMG, PGO, and PGO-epsilon waves) in both sleep and waking states by asking the following questions: l. Will electrical stimulation of CNA alter arousal state and spontaneous PGO wave activity across behavioral states? 2. Will the infusion of serotonergic (5-HT), adrenergic drugs or corticotropin releasing factor (CRF) into CNA alter arousal state and PGO wave generation? The 5-HT and NA systems are prominent in CNA, are important in REM and have demonstrated roles in PGO wave generation, and there is a major CRF input into brainstem PGO wave generator regions from CNA. This project will also examine CNA modulation of alerting mechanisms in waking using PGO-epsilon as a measure of activation PGO-epsilon responsiveness will be tested in the basic startle paradigm and in the fear-potentiated startle paradigm (the role of CNA in conditioned fear is demonstrated in the fear-potentiated startle paradigm) to answer the following questions: l. Will electrical stimulation of CNA increase the amplitude of the elicited PGO wave together with that of the acoustic startle reflex (ASR)? 2. Will PGO-epsilon be elicited in the fear-potentiated startle paradigm? and will lesions of CNA blocking fear- potentiated startle similarly block PGO-epsilon? 3. Will pharmacological manipulations of CNA, that increase or decrease ASR and/or fear- potentiated startle, similarly increase or decrease responsivity in brainstem mechanisms underlying PGO-epsilon? The involvement of the amygdala in modulating arousal state and alerting may have bearing on our understanding the dysfunctional emotionality and anxiety associated with many clinical conditions. These studies may also lead to a better understanding of disorders in which REM is altered For example, in narcolepsy, cataplectic attacks are abnormally triggered by emotional stimuli. REM may also be disturbed in posttraumatic stress disorder, which is characterized by hypervigilance to unfamiliar stimuli and stereotypical anxiety dreams.

快速眼动睡眠(REM)期间的大脑活动类似于 高度警觉状态，电生理特征也可见于 警觉唤醒(脑电活动、海马theta和PGO波活动)。 有很好的证据表明，枕膝肌(PGO)波是 REM的定义特征及其声音诱导的模拟(PGO-epsilon)是 警觉的神经指示器。矛盾的是，在快速眼动过程中，大脑机制 的警报在很大程度上是同时被内源性激活的 未知的机制阻止了大脑活动转化为 行为唤醒。 杏仁核可能在调节觉醒和产生 警觉、唤醒和快速眼动的许多常见功能。中央核 杏仁核(CNA)突出地直接投射到脑干区域 在REM波和PGO波的产生中很重要。因此，中央通讯社提供了一个 边缘系统可能影响警报机制和 行为状态；而且这种影响可能是一个重要的 REM诱导和维护中的因素。 本项目将研究CNA对白化病觉醒和警报的调节 使用标准指标(EEO、EMG、PGO和PGO-epsilon波)的大鼠 睡眠和清醒状态，通过问以下问题：L。将 电刺激CNA改变觉醒状态和自发性PGO波 跨行为状态的活动？2.注射5-羟色胺能 5-羟色胺、肾上腺素能药物或促肾上腺皮质激素释放因子(CRF)进入CNA 改变觉醒状态和PGO波的产生？5-羟色胺和NA系统是 在CNA中突出，在REM中非常重要，并在PGO中发挥了重要作用 脑干PGO波有CRF的主要输入 来自CNA的生成器区域。本项目还将研究CNA调制 以PGO-epsilon作为衡量觉醒状态的警报机制 激活PGO-epsilon反应性将在基本惊吓中进行测试 范式和在恐惧强化的惊吓范式中(CNA在 条件性恐惧在恐惧强化的惊吓范式中表现出来) 回答以下问题：L。会不会电刺激中央社 增加引出的PGO波的幅度与 声惊厥反射(ASR)？2.PGO-epsilon是否会在 恐惧强化的惊吓范例？以及CNA的损伤是否会阻止恐惧- 加强的惊吓同样阻断了PGO-epsilon？3.药理作用 对CNA的操纵，增加或减少ASR和/或恐惧- 加强惊吓，同样增加或减少对 PGO-epsilon的脑干机制？ 杏仁核参与调节觉醒状态和警觉 可能会影响我们对失调性情绪的理解 与许多临床症状相关的焦虑。这些研究还可能 有助于更好地理解REM被改变的障碍 例如，在发作性睡病中，痉挛发作是由 情感刺激。快速眼动也可能在创伤后应激障碍 精神障碍，其特征是对陌生刺激高度警惕 和刻板印象中的焦虑梦。