MECHANISMS AND REGULATION OF 5-HT RECEPTORS IN THE CNS

5-羟色胺(5-羟色胺，5-HT)是一种重要的神经递质 大脑。自从40多年前发现它以来，许多研究都 确定了它在神经系统中的分布，参与其中的机制 它的合成和降解以及调节其释放的因素。 最近的研究主要集中在了解受体上。 5-羟色胺使用的亚型及其受体的作用机制 发出他们行动的信号。这些研究很重要，因为它们提供了 了解5-羟色胺作用机制的分子框架 在正常的大脑中起作用。此外，它们还提供了一扇了解 5-羟色胺能功能异常如何对神经系统和 精神疾病。 PI实验室的长期目标是了解这些行动 中枢神经系统中不同5-羟色胺受体亚型的信号传递 系统以及这种信号传递背后的离子和分子机制。 此应用程序建议在 通过阐明5-羟色胺的作用机制 5-HT4亚型受体增加了膜的兴奋性。这些 研究将在体外脑片中使用电生理技术 并将研究cAMP信号级联的可能作用 作为特定离子电流在介导5-HT4反应中的作用 大脑。 这项工作将有助于我们对5-羟色胺能功能的理解。 健康和疾病状态被认为涉及5-羟色胺能 顽固性疼痛、抑郁、强迫症等功能障碍 混乱和自杀。此外，预计这项工作将 为开发新的药物治疗方法做出贡献 针对5-羟色胺能系统的干预。

Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter in the brain. Since its discovery, more than 40 years ago many studies have defined its distribution in the nervous system, the mechanisms involved in its synthesis and degradation and the factors that regulate its release. More recent studies have concentrated on understanding the receptor subtypes used by serotonin and the mechanisms by which these receptors signal their actions. These studies are important since they provide the molecular framework for understanding the mechanisms by which serotonin acts in the normal brain. Moreover they provide a window for understanding how abnormal serotonergic function can contribute to neurological and psychiatric conditions. The long term goal of the PI's laboratory is to understand the actions signaled by different serotonin receptor subtypes in the central nervous system and the ionic and molecular mechanisms underlying this signaling. This application proposes to continue work initiated by the PI during the previous funding cycle by elucidating the mechanisms by which serotonin receptors of the 5-HT4 subtype increase membrane excitability. These studies will use electrophysiological techniques in in vitro brain slices and will examine the possible role of the cAMP signaling cascade as well as the role of specific ionic currents in mediating 5-HT4 responses in the brain. This work will contribute to our understanding of serotonergic function in health and also in disease states thought to involve serotonergic dysfunction such as intractable pain, depression, obsessive compulsive disorder and suicide. Moreover it is anticipated that this work will contribute to the development of novel pharmacological therapeutic interventions aimed at serotonergic systems.