NEURAL SUBSTRATES OF AROUSAL AND EMOTION

这个应用程序旨在更好地了解大脑如何 5-羟色胺系统在正常情况下起作用。 只有通过这样一个 我们将能够理解（和改善）它是如何 功能障碍表现为多种临床病理学，包括， 抑郁、焦虑、强迫症和肌阵挛。 为了达到必要的实验精度水平， 拟议的实验集中在行为动物的单细胞记录上。 以前的研究已经描述了脑内多巴胺能神经元的活动， 神经元在睡眠-觉醒-觉醒周期中的作用，以及它们对 各种环境和生理挑战。 拟议 研究将把这些分析扩展到检查 这些神经元在复杂的哺乳动物行为中的作用。 特别是，飞行员 实验表明，嘴侧（脑桥）的多巴胺能神经元 中缝群在中枢模式期间被显著激活（2-5倍） 发生器（CPG）介导的节律行为，特别是那些涉及 口颊反应（咀嚼、舔、梳理）。 反过来， 许多（所有）相同神经元的活动在 定向反应（如头部和眼睛运动、海马体所示） θ活动、PGO波和心率减速）。 这些初步观察结果将受到严格测试，并扩展到 包括尾侧（髓质）组的多巴胺能神经元。 三套 的研究提出，利用单单位记录，多管 微离子电渗和体内脑微透析。 I）血清素能的 神经元活动和CPG介导的行为。 （一）确定性 脑桥钙能神经元的活性与脑梗死的发生呈正相关， 神经元和节律行为，特别是那些涉及口颊 地区？ B）髓质群的多巴胺能神经元是否显示出 与不包括口颊的节律行为的关系 运动，但这确实包括由更多尾部方面介导的运动 神经轴的位置吗 c）CPG相关的神经元活动增加 伴随着血清素释放的增加， 与行为直接相关的区域？ II）血清素能的 定向反应的神经元活动。 a）确定的逆 脑桥活动与脑桥活动存在相关性，而脑桥活动与脑桥活动无关， 能神经元和定向行为？ B）这种减少是否 与眼睛或头部运动有关的神经元活动，还是与传入输入有关的神经元活动？ III）体树突自身受体对5-羟色胺能神经元 生理条件下的活动。

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.