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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在我们最初的实验中，我们专注于增加我们的试点数据的样本量，以控制BLA神经元对5-羟色胺受体激活的突触后反应，以及通过突触前5-羟色胺受体激活来修改突触传递。在这些实验中，我们检测了BLA投射神经元和中间神经元对外源性5-羟色胺的突触后反应(目标1)。这些研究结果表明，应用5-羟色胺可引起BLA主神经元突触前谷氨酸释放显著减少(为基线的54%)，这是通过激活5-HT1B受体介导的。值得注意的是，这一作用被预先应用测试化合物GSK1完全阻断。正如早期研究预测的那样，5-羟色胺还通过兴奋局部环路中间神经元而间接抑制主神经元，从而增加GABA的紧张性释放。在少数细胞中，5-羟色胺还直接引起5-HT1a受体介导的主神经元抑制，而主神经元似乎对GSK1不敏感。与这些研究相结合，我们还对另外12个BLA投射神经元进行了单细胞RT-PCR研究，以证实我们对该细胞群中5HT受体mRNA表达的初步观察。

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.