Abstracts

RATIONALE: An imbalance of synaptic excitation and inhibition in the hippocampus has been hypothesized to contribute to epilepsy. Hypotheses about loss or dormancy of inhibitory interneurons, and the consequences of synaptic reorganization, have been debated. In this preliminary study, we examined inhibition with whole-cell recordings from hippocampal slices in the kainate-treated rat model of temporal lobe epilepsy.
METHODS: Hippocampal slices were prepared 5-9 months after kainate treatment, when rats were observed to have a high frequency of spontaneous motor seizures. Spontaneous inhibitory postsynaptic currents (sIPSCs) from dentate granule cells and CA1 pyramidal neurons were recorded using: (1) CsCl-containing pipets and holding potential at -70 mV in DNQX (50[mu] M) and AP-5 (50[mu] M), and (2) Cs-gluconate-containing pipets and holding potential at 0 mV in ACSF. Miniature IPSCs (mIPSCs) were obtained by adding TTX (1[mu] M).
RESULTS: In preliminary data, all 14 granule cells from kainate-treated rats recorded with CsCl pipets invariably exhibited large (up to hundreds pA) and frequent sIPSCs. Application of TTX revealed highly frequent mIPSCs with medium-to-large amplitudes. Similarly, 7 granule cells recorded with Cs-gluconate also expressed large and frequent sIPSCs both in ACSF and in DNQX (50 [mu] M) plus AP-5 (50 [mu] M). The mIPSCs were also frequent. In CA1, most pyramidal neurons (11 of 12, from same rats used for granule-cell recordings) also exhibited frequent sIPSCs, but their amplitudes were considerably smaller than those of granule cells. In 9 of 11 neurons, the mIPSCs were small but frequent.
CONCLUSIONS: These preliminary data, based on sIPSCs and mIPSCs, suggest a vigorous hippocampal inhibition (at least in the dentate gyrus) of rats with kainate-induced epilepsy. The properties of this inhibition, and its hypothetical role in epilepsy, remain to be explored.
[Supported by: NS 16683]