NEURAL SUBSTRATES OF AROUSAL AND EMOTION

唤醒和情绪的神经基础

基本信息

批准号：
2244093
负责人：
BARRY L JACOBS
金额：
$ 21.16万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-06-01 至 1996-06-30
项目状态：
已结题

项目摘要

This application is directed at better understanding how the brain serotonin system functions under normal conditions. Only through such an understanding will we be able to appreciate (and ameliorate) how its dysfunction is manifested in a variety of clinical pathologies, including, depression, anxiety, obsessive-compulsive disorders, and myoclonus. In order to achieve a necessary level of experimental precision, the proposed experiments focus on single cell recordings in behaving animals. Previous studies have characterized the activity of brain serotonergic neurons across the sleep-wake-arousal cycle, and their response to a variety of environmental and physiological challenges. The proposed studies will extend these analyses to an examination of the activity of these neurons during complex mammalian behavior. In particular, pilot experiments indicate that serotonergic neurons in the rostral (pontine) raphe groups are dramatically activated (2-5 fold) during central pattern generator (CPG) mediated rhythmic behaviors, especially those involving oral-buccal responses (chewing, licking, grooming). Reciprocally, the activity of many (all) of the same neurons is strongly inhibited during orienting responses (as indicated by head and eye movements, hippocampal theta activity, PGO waves, and heart rate deceleration). These initial observations will be tested rigorously, and expanded to encompass the caudal (medullary) group of serotonergic neurons. Three sets of studies are proposed, utilizing single unit recordings, multibarrel microiontophoresis, and in vivo brain microdialysis. I) SEROTONERGIC NEURONAL ACTIVITY AND CPG MEDIATED BEHAVIORS. a) Does a definitive positive relationship exist between the activity of pontine serotonergic neurons and rhythmic behaviors, especially those involving the oral-buccal region? b) Do the medullary groups of serotonergic neurons display a relation to rhythmic behaviors which does not include oral-buccal movements, but that does include movements mediated by more caudal aspects of the neuraxis? c) Are CPG-related increases in neuronal activity accompanied by increased release of serotonin preferentially in those brain regions directly related to the behavior? II) RELATION OF SEROTONERGIC NEURONAL ACTIVITY TO ORIENTING RESPONSES. a) Does a definitive inverse relationship exist between the activity of pontine, but not medullary, serotonergic neurons and orienting behavior? b) Is this decrease in neuronal activity related to eye or head movements, or to afferent inputs? III) ROLE OF THE SOMATODENDRITIC AUTORECEPTOR UPON SEROTONERGIC NEURONAL ACTIVITY UNDER PHYSIOLOGICAL CONDITIONS.

该应用程序是为了更好地了解大脑的方式 5-羟色胺系统在正常条件下起作用。只有通过这样的理解我们将能够欣赏（和改善）如何功能障碍表现为多种临床病理，包括抑郁，焦虑，强迫症和肌阵挛。为了达到必要的实验精度，建议的实验集中于行为动物中的单细胞记录。先前的研究表征了脑血清素能的活性整个睡眠效果周期的神经元，它们对各种环境和生理挑战。提议研究将把这些分析扩展到研究这些神经元在复杂的哺乳动物行为中。特别是飞行员实验表明罗斯塔尔（Pontine）中的血清素能神经元中央模式期间，raphe组被大大激活（2-5倍）发电机（CPG）介导的节奏行为，尤其是涉及的节奏行为口服 - 核反应（咀嚼，舔，修饰）。相互在许多（全）同一神经元的活性中都受到强烈抑制定向响应（如头部和眼睛运动所示，海马 theta活动，PGO波和心率减速）。这些最初的观察结果将进行严格测试，并扩展到涵盖了5-颈源性神经元的尾（髓质）组。三组提出了研究的研究，利用单个单位记录，多领微滴虫和体内脑微透析。 i）血清素能神经元活性和CPG介导的行为。 a）做一个确定的蓬丁血清素能的活性之间存在正相关关系神经元和节奏行为，尤其是涉及口腔核的行为地区？ b）做血清素能神经元的髓样组显示与不包括口腔 - 核的节奏行为有关运动，但这确实包括由更尾部方面介导的运动神经？ c）神经元活性与CPG相关的增加伴随着在这些大脑中优先释放5-羟色胺与行为直接相关的区域？ ii）血清素能的关系神经元活动对定向反应。 a）做一个确定的逆蓬托的活动之间存在关系，但不存在于髓质血清素能神经元和定向行为？ b）这种减少是与眼睛或头部运动有关的神经元活动，还是传入的输入？ iii）体体自身受体在5-羟色胺能神经元上的作用生理条件下的活动。