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

描述：前额叶皮层（PFC）在认知和 情感功能PFC电路中的功能障碍与以下因素密切相关： 精神分裂症的病理生理学，特别是在表达 阴性症状。非典型抗精神病药物如氯氮平 改善这些负面症状已经把注意力集中在血清素上 （5-HT）以及PFC内的多巴胺（DA）调节系统，因为这些 药物是5-HT和DA受体的有效拮抗剂。尽管 这两种神经调节系统在调节PFC神经元中的重要性 活性，很少有人知道他们如何影响离子电导 在PFC细胞内形成信息处理。此外，几乎没有什么是 已知5-HT和DA如何在单个PFC神经元水平上相互作用。到 为了解决这些问题，提出了一项研究和培训计划， 电生理学、药理学和分子生物学的结合 技术实现两个具体目标。第一是考察 5-HT_（2a/c）受体激动对急性分离PFC神经元Na ~+电流的影响 并表征介导的信号级联。第二个目标是 研究了5-HT_（2a/c）与DA_（1/5）相互作用的性质和机制 将检查Na+电流的信号传导途径。实现这些 aims将提供必要的重要信息， PFC功能的综合模型以及功能失调的状态， 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.