MECHANISMS AND REGULATION OF 5HT RECEPTORS IN THE CNS

5-羟色胺是哺乳动物体内普遍存在的一种神经递质 大脑。因此，它被牵连到控制着许多 行为和精神疾病的病理生理学，如 抑郁症和强迫症。一直以来都是 认识到5-羟色胺通过多种受体发挥作用 在大脑中发挥作用的亚型。因此很具体 5-羟色胺受体亚型一直被认为是很有前途的 治疗干预的靶点。努力实现这些目标 然而，干预受到我们有限的理解的阻碍。 不同5-羟色胺受体亚型介导的作用 在大脑里。这项提案旨在通过以下方式解决这一问题 两种5-羟色胺受体作用机制的研究 介导5-羟色胺兴奋性反应的亚型 大脑。 5-羟色胺对体外大鼠脑片的影响 使用全细胞记录电生理进行研究 技巧。具体地说，我们将调查 5-羟色胺使丘脑前部神经元去极化和 前额叶皮质。我们假设这些表面上 类似的反应涉及两种不同的5-HT7受体 和5-H_2A亚型。此外，我们假设 这些反应也将通过不同的细胞 和离子机制。 这些研究应该阐明特定的 5-羟色胺受体亚型调节膜兴奋性 中枢神经系统。因此，他们应该为我们的 了解5-羟色胺在大脑中的作用。这 事实证明，知识应该有助于指导 针对5-羟色胺能系统的新治疗策略 大脑。

Serotonin is a ubiquitous neurotransmitter in the mammalian brain. As such it has been implicated in the control of many behaviors and in the pathophysiology of mental diseases such as depression and obsessive compulsive disorders. It has long been recognized that serotonin acts through a variety of receptor subtypes to exert its effects in the brain. Thus specific serotonin receptor subtypes have long been regarded as promising targets for therapeutic intervention. Efforts to implement such interventions, however, are hampered by our limited understanding of the actions mediated by different serotonin receptor subtypes in the brain. This proposal seeks to address this issue by elucidating the mechanism of actions of two serotonin receptor subtypes that mediate excitatory responses to serotonin in the brain. The effects of serotonin in in vitro rat brain slices will be investigated using whole cell recording electrophysiological techniques. Specifically we will investigate the ability of serotonin to depolarize neurons of the anterior thalamus and prefrontal cortex. We hypothesize that these superficially similar responses involve two different receptors of the 5-HT7 and 5-H2A subtypes respectively. Furthermore we hypothesize that these responses will also be mediated though different cellular and ionic mechanisms. These studies should elucidate the mechanisms by which specific serotonin receptor subtypes regulate membrane excitability in the central nervous system. As such they should contribute to our understanding of the actions of serotonin in the brain. This knowledge should prove helpful in guiding the development of novel therapeutic strategies targeting serotonergic systems in the brain.