Neural Substrates of Arousal and Emotion

描述(申请人提供)：5-羟色胺，一种化学物质 中枢神经系统(CNS)的神经递质，是重要的牵连 在各种人类神经和精神病态中。然而，它的基本 神经生物学作用仍有些模糊。真正领略到 5-羟色胺在疾病过程中的作用及其治疗，前提是 了解其在正常哺乳动物生理和行为中的作用。至 为此，本研究旨在加深对基本知识的了解 中枢5-羟色胺系统的功能主要通过记录 行为动物脑内5-羟色胺神经元的电活动。录音 将在5-羟色胺神经元的吻部/上升组(在 中缝背核)以及尾侧/降支群(在核内 暗中缝和苍白球)。建议的研究是根据我们的 5-羟色胺神经元活性与 行为激活/紧张性运动活动的水平，尤其是 重复运动活动(中枢模式产生器调节)。两大 提出了一组实验：1)环境和行为因素 可能会调节这些脑细胞的基本活动，而 调节这些效应的神经化学物质；2)大脑5-羟色胺的作用 中枢疲劳中的神经元。后一个问题的重要性源于 疲劳被认为是许多因素中的重要组成部分 疾病过程(例如，慢性疲劳综合征、多发性硬化症和 抑郁)。除了对动物行为的单一单元记录外， 实验将采用：1)体内脑5-羟色胺的微透析措施 和多巴胺；2)反相微渗析局部给药； 3)c-Fos表达(结合双重标记)作为一种指标 在特定条件下激活的5-羟色胺神经元；以及4) 计算机生成的尖峰序列分析。

DESCRIPTION (provided by applicant): Serotonin, acting as a chemical neurotransmitter in the central nervous system (CNS), is importantly implicated in a variety of human neuro- and psychopathologies. However, its basic neurobiological role remains somewhat obscure. A true appreciation of how serotonin functions in disease processes, and treatment of them, presupposes an understanding of its actions in normal mammalian physiology and behavior. To that end, the present research is aimed at furthering knowledge of the basic functioning of the CNS serotonin system primarily through recording the electrical activity of brain serotonin neurons in behaving animals. Recordings will be made in both the rostral/ascending group of serotonin neurons (in the dorsal raphe nucleus) as well as the caudal/descending group (in the nuclei raphe obscurus and pallidus). The proposed studies are an outgrowth of our basic hypothesis that the activity of serotonin neurons is closely linked to level of behavioral activation/tonic motor activity, and especially to repetitive motor activity (central pattern generator-mediated). Two major groups of experiments are proposed: 1) environmental and behavioral factors that may modulate the basic activity of these brain cells, and the neurochemicals that mediate these effects; 2) the role of brain serotonin neurons in central fatigue. The importance of this latter issue derives from the fact that fatigue is considered an important component in a number of disease processes (e.g., chronic fatigue syndrome, multiple sclerosis, and depression). In addition to single unit recordings in behaving animals, the experiments will employ: 1) In vivo microdialysis measures of brain serotonin and dopamine; 2) Local drug administration by means of reverse microdialysis; 3) c-Fos expression (in conjunction with double labeling) as an indicator of serotonin neurons activated under specific conditions; and 4) Computer-generated spike train analyses.