EMORY-MSSM-GSK-NIMH COLLABORATIVE MOOD AND ANXIETY DISORDERS INITIATIVE

埃默里-MSSM-葛兰素史克-NIMH 情绪和焦虑症合作倡议

• 批准号: 8357558
• 负责人: DONALD G RAINNIE
• 金额: $ 4.12万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357558
• 关键词: Anxiety Disorders; Cells; Data; Funding; Glutamates; Grant; Interneurons; Mediating; Modification; Mood Disorders; National Center for Research Resources; National Institute of Mental Health; Neurons; Population; Primates; Principal Investigator; Receptor Activation; Research; Research Infrastructure; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sample Size; Serotonin; Serotonin Receptor 5-HT1A; Serotonin Receptor 5-HT1B; Source; Synaptic Transmission; Testing; United States National Institutes of Health; cost; gamma-Aminobutyric Acid; mRNA Expression; postsynaptic; presynaptic; receptor; research study; response; serotonin receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In our initial experiments we focused on increasing the sample size of our pilot data for the control postsynaptic response of BLA neurons to serotonin receptor activation, as well as the modification of synaptic transmission by presynaptic serotonin receptor activation. For these experiments, we examined the postsynaptic response of BLA projection neurons and interneurons to exogenous application of 5HT (Aim 1). The results of these studies show that 5-HT application causes a significant reduction of presynaptic glutamate release (54% of baseline) onto BLA principal neurons, which is mediated by activation of 5-HT1B receptors. Significantly, this action was fully blocked with prior application of the test compound, GSK1. As predicted by earlier studies, 5-HT also caused an indirect inhibition of principal neurons by exciting local circuit interneurons thereby increasing tonic GABA release. In a few cells, 5-HT also caused a direct 5-HT1A receptor-mediated inhibition in principal neurons, which appeared to be insensitive to GSK1. In association with these studies we also conducted a single cell RT-PCR study on an additional 12 BLA projection neurons to confirm our preliminary observations on 5HT receptor mRNA expression in this cell population.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在最初的实验中，我们专注于增加BLA神经元对5-羟色胺受体激活的突触后反应的样本量，以及通过突触前血清素受体激活对突触传播的修饰。对于这些实验，我们检查了BLA投射神经元和中间神经元对5HT外源应用的突触后反应（AIM 1）。 这些研究的结果表明，5-HT应用会导致突触前谷氨酸释放（基线的54％）显着降低BLA主神经元，这是通过5-HT1B受体的激活介导的。值得注意的是，该动作通过先前应用测试化合物GSK1完全阻止。正如较早的研究所预测的那样，5-HT还通过激发局部回路中间神经元，从而增加了对主要神经元的间接抑制，从而增加了补品GABA释放。 在几个细胞中，5-HT还引起了主要神经元中直接的5-HT1A受体介导的抑制作用，这似乎对GSK1不敏感。与这些研究相关，我们还对另外12个BLA投影神经元进行了单个细胞RT-PCR研究，以确认我们对该细胞群中5HT受体mRNA表达的初步观察结果。