Neurosteroid regulation of inhibitory synaptic transmission in the rat hippocampus in vitro

The effect of the neurosteroid dehydroepiandrosterone sulfate on inhibitory synaptic transmission was studied in area CAI of the rat hippocampus using an in vitro hippocampal slice preparation. Synaptic responses elicited by stimulation of Schaffer collateral fibers were recorded extracellularly as population spikes in the somatic region and as synaptic field potentials in the dendritic region. Bath application of dehydroepiandrosterone sulfate ( 10 mu M) enhanced the synaptically evoked somatic population spike with no effect on the dendritic synaptic potential. Isolation of the alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptor-mediated component of the s ynaptic response by addition of antagonists of N-methyl-D-aspartate and GAB A receptors to the perfusion saline demonstrated that dehydroepiandrosteron e sulfate had no effect on this component of the dendritic synaptic potenti al. In contrast, dehydroepiandrosterone sulfate antagonized GABA receptor-m ediated inhibitory effects in the somatic region, resulting in an augmentat ion of the somatic population spike amplitude. Paired-pulse facilitation wa s unaltered by dehydroepiandrosterone sulfate, thus arguing against possibl e presynaptic sites of dehydroepiandrosterone sulfate's actions. These results indicate that dehydroepiandrosterone sulfate can alter synapt ic transmission in the hippocampus through selective postsynaptic actions o n inhibitory synaptic transmission. A synaptic effect of dehydroepiandroste rone sulfate is consistent with a neuromodulatory role for this neurosteroi d in the central nervous system, and may contribute to the reported effects of dehydroepiandrosterone sulfate on cognitive processes such as learning and memory. (C) 1999 IBRO. Published by Elsevier Science Ltd.