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

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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.