Dehydroepiandrosterone sulfate alters synaptic potentials in area CA1 of the hippocampal slice

The influences of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) on neuronal properties and synaptic transmission in area CA1 of the hippocampus were examined using a slice preparation. DHEAS had no apparent effects upon cell membrane resistance or active cell responses to intracellular hyperpolarizing or depolarizing current pulses. However, DHEAS did increase the excitability of CA1 neurons in response to Schaffer collateral synaptic stimulation. This was apparent both in field potential recordings as well as intracellular recordings. Effects appeared within minutes following exposure to DHEAS and were reversible, suggesting a non-genomic mechanism of action. Intracellular recordings indicated that DHEAS increased the amplitudes of EPSPs associated with stimulation of Schaffer collateral fibers. The increased EPSP amplitudes resulted from DHEAS effecting an inhibition of fast IPSPs as well as a direct enhancement of excitatory synaptic transmission. No significant effects on slow IPSPs were noted. In summary, neurosteroids such as DHEAS may influence synaptic transmission through multiple mechanisms. Such influences result in increased excitability of postsynaptic neurons and indicate the profound influences neurosteroids may have to regulate neuronal activity in intact CNS structures.