Topography of Serotonin Dysfunction

项目摘要 人们对血清素在大脑中的循环机制仍知之甚少 抑郁症、药物成瘾和其他疾病的功能障碍。了解 5-羟色胺神经传递在精神病理学中的作用是复杂的， 5-羟色胺系统最显著的特征：它是神经解剖学。在这 项目我们研究如何血清素神经元功能的变化，在动物模型， 抑郁症和尼古丁戒断，以及抗抑郁药治疗后。我们 这项工作旨在协调行为药理学和神经解剖学， 一些相互矛盾的发现。最重要的假设是， 5-羟色胺的激活有着地形学上的组织变化 抑郁症中的神经元，这些都通过抗抑郁药治疗解决。在 此外，我们还研究了5-HT 1A受体介导的反馈抑制 变化的协调与改变的模式，神经元的活动。最后 我们研究了地形选择性变化的功能影响， 行为的激活状态。具体目标是将蜂窝、系统和 5-羟色胺功能和功能障碍的行为学研究 神经传递这项研究计划的长期目标是 更好地了解血清素在情感和成瘾中的作用 紊乱

Project Summary It remains poorly understood how serotonin circuits in the brain dysfunction in depression, drug addiction and other disorders. Understanding the role of serotonin neurotransmission in psychopathology is complicated by one of the most salient features of the serotonin system: it¿s neuroanatomy. In this project we examine how serotonin neuron function changes in animal models of depression and nicotine abstinence, and after antidepressant treatment. Our work seeks to reconcile behavioral pharmacology with neuroanatomy to resolve some of the contradictory findings in the field. The over-riding hypothesis is that there are topographically organized changes in the activation of serotonin neurons in depression and these are resolved by antidepressant treatment. In addition, we examine how feedback inhibition mediated by 5-HT1A receptors changes in coordination with altered patterns of serotonin-neuron activity. Finally we examine the functional impact of topographically selective changes in activation state on behavior. The specific aims integrate cellular, systems and behavioral approaches to understand function and dysfunction of serotonin neurotransmission. The broad long-term goal of this research program is to provide a better understanding of the role of serotonin in affective and addictive disorders.