Topography of Serotonin Dysfunction

描述（由申请人提供）：人们对血清素回路在抑郁症、药物成瘾和其他疾病中如何发生脑功能障碍仍知之甚少。5 -羟色胺神经传递在精神病理学中的作用，由于5 -羟色胺系统的一个最显著的特征：它的神经解剖学而变得复杂。在这个项目中，我们研究了抑郁和尼古丁戒断的动物模型以及抗抑郁药物治疗后血清素神经元功能的变化。我们的工作旨在调和行为药理学与神经解剖学，以解决该领域一些相互矛盾的发现。最重要的假设是，在抑郁症中血清素神经元的激活中存在有组织的地形变化，这些变化可以通过抗抑郁药物治疗来解决。此外，我们还研究了5-HT1A受体介导的反馈抑制如何随着血清素-神经元活动模式的改变而协调变化。最后，我们研究了激活状态的地形选择性变化对行为的功能影响。具体目标是整合细胞，系统和行为方法来了解血清素神经传递的功能和功能障碍。这项研究计划的长期目标是更好地了解血清素在情感障碍和成瘾性障碍中的作用。

DESCRIPTION (provided by applicant): 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: its 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.