It has become increasingly evident in the last decade that gonadal steroid hormones and their metabolites can modulate neuronal activity via non- genomic, short-latency effects. Although there are a significant number of studies that describe the mechanisms of the short-latency effects of the progestins and estrogens, little is known about the mechanisms by which the androgen, testosterone, produces rapid effects in the central nervous system. The goal of this project is to investigate the cellular mechanisms by which testosterone produces direct, short-latency changes in neuronal activity. We will study these mechanisms in the hippocampus, a region of the brain in which testosterone has been demonstrated to produce rapid alterations (within minutes) in neuronal activity. Our overall objective will be to investigate the mechanisms by which testosterone modulates the evoked field potential in the CA1 pyramidal cell layer of the in vitro hippocampal slice. We will use the blind, whole-cell, patch-clamp technique in the in vitro hippocampal slice to: 1) determine if testosterone or one of its active metabolites, dihydrotestosterone, alters passive membrane properties in Ca1 pyramidal cells, and 2) determine if testosterone or dihydrotestosterone modulates synaptic transmission in CA1 pyramidal cells. The results of these studies should provide us with further insights into the means by which gonadal steroids modulate both normal and pathological processes in the central nervous system.
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