AMYGDALAR MODULATION OF BRAINSTEM ALERTING MECHANISMS

脑干警报机制的杏仁核调节

• 批准号: 2274596
• 负责人: LARRY D SANFORD
• 金额: $ 9.11万
• 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/2274596
• 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，电生理特征也存在于 警觉醒来（脑电图激活、海马θ和 PGO 波活动）。 有充分的证据表明，斑膝枕枕叶 (PGO) 波是一种 REM 的定义特征及其声音引发的模拟 (PGO-epsilon) 是 警报的神经指标。矛盾的是，在快速眼动睡眠期间，大脑机制 的警报同时被内源激活 未知的机制阻止大脑活动转化为 行为唤醒。 杏仁核可能在调节唤醒和产生 提醒清醒和快速眼动睡眠的许多常见功能。中央核 杏仁核 (CNA) 明显直接投射到脑干区域 对于 REM 和 PGO 波的产生很重要。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；这种影响可能是重大的 REM 诱导和维持的因素。 该项目将研究 CNA 对白化病患者的唤醒和警报的调节 大鼠在两种情况下均使用标准指数（EEO、EMG、PGO 和 PGO-epsilon 波） 通过询问以下问题来了解睡眠和清醒状态： l．将要 CNA 的电刺激改变唤醒状态和自发 PGO 波 跨行为状态的活动？ 2.能否输注血清素 (5-HT)、肾上腺素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 中很重要，并且在 PGO 中发挥了作用 波产生，并且有一个主要的CRF输入到脑干PGO波 来自 CNA 的生成器区域。该项目还将研究 CNA 调制 使用 PGO-epsilon 作为衡量醒来时警报机制的方法 激活 PGO-epsilon 反应性将在基本惊吓中进行测试 范式和恐惧增强惊吓范式（CNA 在 条件性恐惧在恐惧增强惊吓范式中得到了证明） 回答下列问题： l．会电刺激CNA吗 增加引起的 PGO 波的振幅以及 听觉惊吓反射（ASR）？ 2. PGO-epsilon 是否会被引出？ 恐惧增强的惊吓范式？ CNA 的损伤会阻止恐惧- 强化惊吓同样可以阻断 PGO-epsilon？ 3. 药理作用 操纵 CNA，增加或减少 ASR 和/或恐惧- 增强惊吓，同样增加或减少反应性 PGO-epsilon 的脑干机制？ 杏仁核参与调节唤醒状态和警报 可能会影响我们对功能失调的情绪的理解 焦虑与许多临床病症有关。这些研究也可能 有助于更好地理解 REM 改变的疾病 例如，在发作性睡病中，猝倒发作是由以下因素异常触发的： 情绪刺激。快速眼动睡眠也可能因创伤后压力而受到干扰 障碍，其特征是对不熟悉的刺激过度警惕 和刻板的焦虑梦。