ANALYSIS OF THE KINETICS OF SYNAPTIC INHIBITION POINTS TO A REDUCTIONIN GABA RELEASE IN AREA CA1 OF THE GENETICALLY EPILEPTIC MOUSE, EL

In order to determine whether changes in synaptic inhibition are invol ved in chronic models of epilepsy, it is necessary to understand the f actors which determine the kinetics of fast gamma-aminobutyric acid (G ABA)ergic inhibition. For this purpose, we analyzed the decaying phase of isolated inhibitory postsynaptic currents (IPSC) in rat CA1 pyrami dal cells. Reduction of GABA release (by reducing [Ca2+](o) or paired- pulse stimulation) or blockade of GABA uptake (with tiagabine) led to the conclusion that small changes in the amount of GABA available for postsynaptic binding have Little effect on the peak amplitude, but hav e marked effect on the duration of the IPSC. We then studied isolated GABA(A) receptor-mediated inhibition in area CA1 of the El mouse strai n, which is genetically predisposed to epilepsy. Results were compared with the non-epileptogenic mother strain, ddY. Inhibitory postsynapti c potentials (IPSPs) in El mice (IPSPEl) were not significantly differ ent in amplitude of those from ddY mice (IPSPddY). However, the rise-t ime and duration of IPSPEl were respectively about 25% and 50% shorter than those of IPSPEl. With appropriate pharmacological manipulation o f GABA release or uptake, IPSPEl could be made to resemble the IPSPddY and vice versa. It is concluded that the synaptic release of GABA in area CA1 of the El mouse is decreased compared to that of the ddY mous e.