Regulation of Dorsal and Median Raphe Neural Activity

背侧和中缝神经活动的调节

• 批准号: 6327112
• 负责人: SHERYL G BECK
• 金额: $ 8.5万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6327112
• 关键词: bioassay; brain cell; computer data analysis; corticosteroids; corticotropin releasing factor; dorsal raphe nucleus; electrodes; electrophysiology; evoked potentials; hippocampus; immunocytochemistry; laboratory rat; neurons; neuropharmacology; neuroregulation; radioimmunoassay; receptor expression; serotonin; serotonin receptor; soma; tissue /cell culture

The 5-hydroxytryptamine (5-HT, serotonin) neurotransmitter system maintains many homeostatic functions; it has also been implicated in the etiology and treatment of neurological and affective disorders, such as depression, anxiety, obesity, anorexia, and Alzheimer's disease. One of the PI's primary areas of interest is to understand the cellular mechanisms underlying the etiology and treatment of affective disorders. In the past the PI has focused on characterizing normal hippocampal neural activity and the changes in that normal physiology by chronic treatment with antidepressants or the "stress" hormone corticosterone. The working hypothesis is that the actions of the drugs or mechanism underlying pathological status is due to differential modification of cellular properties or components of the 5-HT neurotransmitter system. In support of this hypothesis chronic treatment with corticosterone or fluoxetine was found to alter hippocampal pyramidal cell neural activity by changing basic cell properties as well as postsynaptic 5-HT receptor mediated responses. As predicted, the nature of the modulatory effects of the chronic treatments are not the same in the CA1 and CA3 subfields. Another likely target for differential modifications in the 5-HT neurotransmitters system is at the level of the 5-HT cell bodies. The median (MR) and dorsal raphe (DR) are the principal sites where 5-HT cell bodies are located. These two nuclei provide the majority of the 5-HT innervation of the forebrain. Even though they share many of the same features, differences between these two nuclei have been identified. The goal of the experiments outlined in this application is to set up a raphe brain slice preparation maintained in vitro to delineate both the common and disparate features of MR and DR cell neural activity. The development of the raphe brain slice will expand the depth of the PIs research focus. The use of the raphe (5-HT cell body) and hippocampal (5-HT fiber projection area) slice preparations in conjunction will provide a mechanism for a more systematic approach to the analysis of the normal physiology and pathophysiological processes of the 5-HT neurotransmitter system.

5-羟色胺（5-HT，5-羟色胺）神经递质系统具有许多稳态功能。它也与神经和情感障碍的病因和治疗有关，例如抑郁，焦虑，肥胖，厌食症和阿尔茨海默氏病。 PI感兴趣的主要领域之一是了解情感障碍病因和治疗的细胞机制。过去，PI致力于表征正常的海马神经活性以及通过抗抑郁药或“胁迫”激素皮质酮治疗正常生理学的变化。工作假设是，病理状况的药物或机制的作用是由于5-HT神经递质系统的细胞性质或成分的差异修饰所致。为了支持这种假设的慢性治疗皮质酮或氟西汀，通过改变基本细胞性能以及突触后5-HT受体介导的反应来改变海马锥体细胞神经活性。如前所述，在CA1和CA3子场中，慢性治疗的调节作用的性质并不相同。 5-HT神经递质系统中差异修饰的另一个可能的靶标是5-HT细胞体的水平。中位数（MR）和背侧Raphe（DR）是5-HT细胞体的主要部位。这两个核提供了前脑5-HT神经支配的大部分。即使它们具有许多相同的特征，也已经确定了这两个核之间的差异。本应用程序中概述的实验的目的是在体外维持的Raphe脑切片制剂，以描绘MR和DR Cell神经活动的常见和不同特征。 Raphe脑切片的发展将扩大PIS研究重点的深度。在结合中使用Raphe（5-HT细胞体）和海马（5-HT纤维投影区）切片制剂将为分析5-HT的正常生理学和病理生理过程的更系统的方法提供一种机制神经递质系统。