DEHYDROEPIANDROSTERONE-SULFATE ALTERS SYNAPTIC POTENTIALS IN AREA CA1OF THE HIPPOCAMPAL SLICE

The influences of the neurosteroid dehydroepiandrosterone sulfate (DHE AS) on neuronal properties and synaptic transmission in area CA1 of th e hippocampus were examined using a slice preparation. DHEAS had no ap parent effects upon cell membrane resistance or active cell responses to intracellular hyperpolarizing or depolarizing current pulses. Howev er, DHEAS did increase the excitability of CAI neurons in response to Schaffer collateral synaptic stimulation. This was apparent both in fi eld potential recordings as well as intracellular recordings. Effects appeared within minutes following exposure to DHEAS and were reversibl e, suggesting a non-genomic mechanism of action. Intracellular recordi ngs indicated that DHEAS increased the amplitudes of EPSPs associated with stimulation of Schaffer collateral fibers. The increased EPSP amp litudes resulted from DHEAS effecting an inhibition of fast IPSPs as w ell as a direct enhancement of excitatory synaptic transmission. No si gnificant effects on slow IPSPs were noted. In summary, neurosteroids such as DHEAS may influence synaptic transmission through multiple mec hanisms. Such influences result in increased excitabiIity of postsynap tic neurons and indicate the profound influences neurosteroids may hav e to regulate neuronal activity in intact CNS structures.