AMYGDALAR MODULATION OF BRAINSTEM ALERTING MECHANISMS

脑干警报机制的杏仁核调节

• 批准号: 6283759
• 负责人: LARRY D SANFORD
• 金额: $ 12.45万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 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 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6283759
• 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，电生理特征也见于 警觉觉醒（EEG激活、海马theta和PGO波活动）。 有很好的证据表明，pinto-genicula-ocipital（PGO）波， 快速眼动的定义特征及其声音诱发的类似物（PGO-REM）是 神经系统的警报信号奇怪的是，在快速眼动期间， 在很大程度上被激活的同时， 未知的机制阻止了大脑活动转化为 行为唤起 杏仁核可能在调节觉醒和产生 唤醒和快速眼动的许多共同特征。中央核 杏仁核（CNA）的突出直接投射到脑干区域 在REM和PGO波的产生中起重要作用。因此，CNA提供了 边缘系统可能影响警报机制的途径， 行为状态;而且这种影响可能是一个重要的 快速眼动的诱导和维持。 这个项目将研究CNA调制唤醒和警觉在白化病 大鼠使用标准指标（EEO，EMG，PGO和PGO-EEG波）， 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. 注射肾上腺素能 （5-HT）、肾上腺素能药物或促肾上腺皮质激素释放因子（CRF）进入CNA 改变唤醒状态和PGO波的产生 5-HT和NA系统是 在CNA中突出，在REM中重要，并在PGO中发挥作用 波的产生，并有一个主要的CRF输入到脑干PGO波 CNA的发电机区域。本项目还将研究CNA调制 清醒时的警报机制，使用PGO-ESTA作为衡量 将在基本惊吓中测试激活PGO-PFO响应性 范式和恐惧增强惊吓范式（CNA在 条件性恐惧表现在恐惧增强惊吓范式中） 回答以下问题：l。将电刺激CNA 增加诱发的PGO波的振幅， 听觉惊吓反射（ASR）？2. PGO-BLOOD是否会在 恐惧强化惊吓模式而中枢神经系统的病变会阻断恐惧吗 加强惊吓同样阻止PGO-ESTA？3.将药理学 操纵CNA，增加或减少ASR和/或恐惧- 增强惊吓，类似地增加或减少 脑干机制潜在的PGO-brainstem？ 杏仁核参与调节唤醒状态和警觉 可能会影响我们对功能失调的情绪的理解， 焦虑与许多临床症状有关。这些研究也可能 从而更好地理解快速眼动被改变的疾病。 例如，在嗜睡症中， 情感刺激快速眼动也可能在创伤后应激障碍中受到干扰 一种以对不熟悉的刺激过度警觉为特征的疾病 和典型的焦虑梦