Modulation of BNST 5-HT responses by corticosterone

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DESCRIPTION (provided by candidate): The bed nucleus of the stria terminalis (BNST) is believed to mediate anxiety-like states produced by exposure to uncontrollable, unpredictable, and/or chronic stress. These stressors are associated with long-term elevations in serotonergic (5-HT) and corticosterone release. Many individual BNST neurons exhibit both a 5-HT1A-mediated, anxiolytic, hyperpolarization and a 5-HT2-mediated, anxiogenic, depolarization in response to exogenous 5-HT application. The net response of each cell thus depends on the balance of these two responses. Chronic corticosterone has been shown to decrease 5-HT1A function and increase 5- HT2 function in several brain areas. This action within the BNST should shift the balance of 5-HT responses to favor more 5-HT2-mediated depolarizations, which, when combined with increased 5-HT release, could mediate anxiety. The specific aims in this proposal are designed to determine whether chronic corticosterone shifts the electrophysiological response of BNST neurons to favor 5-HT2-mediated function, and whether chronic corticosterone produces a more anxiogenic behavioral profile to BNST 5-HT.