MODULATION OF SYNAPTIC GABA(A) RECEPTOR FUNCTION BY BENZODIAZEPINES IN AREA CA3 OF RAT HIPPOCAMPAL SLICE CULTURES

The effects of the benzodiazepine agonist midazolam on GABA(A) recepto r-mediated inhibition were investigated in area CA3 of hippocampal sli ce cultures. Midazolam (100 nM) increased the decay time constant (tau (OFF)) Of miniature inhibitory postsynaptic currents (mIPSCs) recorded from pyramidal cells by similar to 40%, but did not significantly aff ect their activation rate or amplitude, consistent with saturation of postsynaptic GABA(A) receptors by a quantum of GABA. Non-stationary va riance analysis of mIPSCs revealed that the unitary conductance of syn aptic GABA(A) channels (similar to 31 pS) was unaffected by midazolam. Midazolam increased not only the tau(OFF) (51%), but also the amplitu de (23%) of unitary IPSPs, recorded from pairs of monosynaptically con nected inhibitory and pyramidal cells. Simulation of unitary IPSPs ind icated that the increased amplitude was primarily due to the slow time constant of pyramidal cells. Finally, the mean amplitude, tau(OFF) an d single-channel conductance of mIPSCs recorded in cultures chronicall y exposed to midazolam (0.1-10 mu M) for 2 weeks were not different fr om control mIPSCs, nor was their response to midazolam. We conclude th at benzodiazepines increase synaptic GABA(A) channel open time, as des cribed previously, and that this results in an increase in both the am plitude and duration of IPSPs in pyramidal cells. Copyright (C) 1996 E lsevier Science Ltd