5-HT Modulation of Na+ Currents in PFC Pyramidal Cells

描述：前额叶皮质(PFC)在认知和发育过程中起重要作用。 情感功能。PFC回路中的功能障碍与 精神分裂症的病理生理学，尤指精神分裂症的表现 阴性症状。非典型抗精神病药物，如氯氮平的能力 改善这些阴性症状将注意力集中在5-羟色胺上 (5-羟色胺)以及前额叶内的多巴胺(DA)调节系统，如下所示 药物是5-羟色胺和多巴胺受体的强有力的拮抗剂。尽管 这两种神经调节系统在PFC神经元调控中的重要性 活性，人们对它们如何影响离子电导知之甚少。 在PFC细胞内进行形状信息处理。此外，几乎没有什么是 已知5-羟色胺和多巴胺如何在单个PFC神经元水平上相互作用。至 为了解决这些问题，提出了一项研究和培训计划，利用 电生理学、药理学和分子生物学的结合 实现两个特定目标的技术。第一个是考察 5-HT2a/c受体对急性分离的PFC神经元钠电流的刺激 并对中介信号级联进行了表征。第二个目标是 5-HT2A/c与DA1/5相互作用的性质和机制 我们将研究钠电流上的信号通路。这些成就的实现 AIMS将提供必要的重要信息，以构建准确、 PFC功能以及功能失调状态的集成模型，如 精神分裂症。

DESCRIPTION: The prefrontal cortex (PFC) plays important roles in cognitive and affective function. Dysfunction within PFC circuitry is strongly implicated in the pathophysiology of schizophrenia, particularly in the expression of negative symptoms. The ability of atypical antipsychotics such as clozapine to ameliorate these negative symptoms has focused attention on the serotonin (5-HT) as well as dopamine (DA) modulatory systems within the PFC, as these drugs are potent antagonists at both 5-HT and DA receptors. Despite the importance of these two neuromodulatory systems in regulating PFC neuronal activity, very little is known as to how they affect the ionic conductances that shape information processing within PFC cells. Moreover, almost nothing is known as to how 5-HT and DA interact at the level of individual PFC neurons. To address these issues, a research and training plan is proposed utilizing a combination of electrophysiological, pharmacological and molecular biological techniques to achieve two specific aims. The first is to examine the effect of 5-HT2a/c receptor stimulation on Na+ currents in acutely isolated PFC neurons and to characterize the mediating signaling cascade. The second aim is to characterize the nature and mechanism of interaction of 5-HT2a/c and DA1/5 signaling pathways on Na+ currents will be examined. The achievement of these aims will provide vital information necessary to construct accurate, integrative models of PFC function as well as dysfunctional states such as schizophrenia.