Miniature inhibitory postsynaptic currents in CA1 pyramidal neurons after kindling epileptogenesis

Miniature inhibitory postsynaptic currents (mIPSCs) were measured in CA1 pyramidal neurons from long-term kindled rats (>6 weeks after they reached the stage of generalized seizures) and compared with controls. A large reduction in the number of mIPSCs was observed in a special group of large mIPSCs (amplitude >75 pA). The frequency of mIPSCs in this group was reduced from 0.042 Hz in controls to 0.027 Hz in the kindled animals. The reduction in this group resulted in a highly significant difference in the amplitude distributions. A distinction was made between fast mIPSCs (rise time <2.8 ms) and slow mIPSCs. Fast mIPSCs, which could originate from synapses onto the soma and proximal dendrites, had significantly larger amplitudes than slow mIPSCs, which could originate from more distal synapses (35.4 +/- 1.1 vs. 26.2 +/- 0.4 pA in the kindled group; means +/- SE). The difference in the value of the mean of all amplitudes and frequency of fast and slow mIPSCs did not reach significance when the kindled group was compared with controls. The mIPSC kinetics were not different after kindling, from which we conclude that the receptor properties had not changed. Nonstationary noise analysis of the largest mIPSCs suggested that the single-channel conductance and the number of postsynaptic receptors was similar in the kindled and control groups. Our results suggest a 40-50% reduction in a small fraction of (peri-) somatic synapses with large or complex postsynaptic structure after kindling. This functionally relevant reduction may be related to previously observed loss of a specific class of interneurons. Our findings are consistent with a reduction in inhibitory drive in the CA1 area. Such a reduction could underlie the enhanced seizure susceptibility after kindling epileptogenesis.