Activity-dependent depression of monosynaptic fast IPSCs in hippocampus: contributions from reductions in chloride driving force and conductance.

Whole-cell recordings techniques were used to record pharmacologically isolated fast inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal neurons from rat hippocampal slices. Repetitive extracellular stimulation up to 10 Hz progressively reduced steady-state fast IPSC amplitude. At low stimulation frequencies (up to 1 Hz), this attenuation was characterized by a positive shift of IPSC reversal potential with no change in IPSC conductance. Above 1 Hz stimulation, fast IPSC depression was associated with changes in both reversal potential and IPSC conductance. Use-dependent depression at low frequencies was prevented when cells were chloride-loaded using cesium chloride based intracellular solutions. These findings suggest that activity-dependent depression of fast IPSCs at low stimulus frequencies results entirely from a reduction in chloride driving force, stemming from intracellular chloride accumulation. Activity-dependent changes in fast IPSC conductance occur only at stimulation rates above 1 Hz.