NEURAL SUBSTRATES OF AROUSAL AND EMOTION

这个应用程序旨在更好地理解大脑如何 5-羟色胺系统在正常情况下起作用。只有通过这样一种 理解我们将能够欣赏(和改善)它是如何 功能障碍表现在各种临床病理中，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， 拟议的实验重点是行为动物的单细胞记录。 以前的研究已经表征了大脑5-羟色胺能的活性 贯穿睡眠-觉醒-觉醒周期的神经元，以及它们对 各种环境和生理挑战。建议数 研究将把这些分析扩展到对 这些神经元在复杂的哺乳动物行为中。特别是，Pilot 实验表明，吻部(桥脑)内的5-羟色胺能神经元 中缝组合在中央模式期间被显著激活(2-5倍) 产生器(CPG)介导的节律行为，尤其是涉及 口腔-口腔反应(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(如头部和眼睛运动所示，海马区 Theta活动、PGO波和心率减速)。 这些初步的观察结果将经过严格的测试，并扩展到 包绕5-羟色胺能神经元的尾侧(延髓)群。三套 提出了利用单单元记录、多管记录 微离子导入和活体脑微透析。一)5-羟色胺能 神经元活动和CPG介导的行为。A)是否有明确的 脑桥5-羟色胺能神经元活性呈正相关 神经元和节律行为，尤其是涉及口腔-口腔的行为 地区？B)5-羟色胺能神经元的延髓群是否显示出 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调节的运动 神经轴的位置吗？C)是否与CPG相关的神经元活动增加 伴随着这些大脑中优先释放的5-羟色胺增加 与行为直接相关的地区？II)5-羟色胺能关系 神经元对定向反应的活动。A)做了一个决定性的反转 脑桥活动之间存在关系，但延髓之间没有关系， 5-羟色胺能神经元与定向行为？B)这一下降是在 神经活动与眼睛或头部运动有关，还是与传入输入有关？ 3)5-羟色胺能神经元上的自体递质受体的作用 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.