EPILEPTIFORM ACTIVITY-INDUCED BY PILOCARPINE IN THE RAT HIPPOCAMPAL-ENTORHINAL SLICE PREPARATION

An in vitro slice preparation of combined hippocampus and entorhinal c ortex from adult rats was used to study the modalities of generation a nd propagation, as well as the pharmacological properties of the epile ptiform activity induced by the muscarinic agonist pilocarpine (10 mu M). Simultaneous field potentials recordings were made from the medial entorhinal cortex and from the dentate gyrus, CA3 and CA1 subfields. Pilocarpine application induced two types of interictal epileptiform d ischarges. The first occurred in the entorhinal cortex and consisted o f bursts of population spikes lasting 408 +/- 135 ms (n = 20 slices) a nd repeating at a rate of 0.26 +/- 0.07 Hz (n = 20); this interictal a ctivity propagated to the hippocampus via the perforant path. The seco nd type was only observed in CA3 and CA1 subfields, had shorter durati on (82 +/- 16 ms; n = 20) and occurred at a higher rare (1.42 +/- 0.7 Hz; n = 20) than the first type. Ictal epileptiform discharges (durati on: 11.5 +/- 4.1 s; rate: 0.002 +/- 0.0009 Hz; n = 10) were also seen in the entorhinal cortex, from where they propagated to the dentate, C A3 and CA1 via the hippocampal trisynaptic loop as revealed by latency analysis and lesion experiments. Ictal and interictal discharges of e ntorhinal origin disappeared in the hippocampal sectors, but continued to occur in the entorhinal cortex following a cut of the perforant pa th (n = 5). Fast interictal discharges observed solely in the hippocam pus originated in CA3, since sectioning the Schaffer collaterals made them disappear in CA1 (n = 7). All types of epileptiform activity disa ppeared during application of the non-N-methyl-D-aspartate receptor an tagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M; n = 7). By con trast, the N-methyl-D-aspartate receptor antagonist 3-3(2-carboxy-pipe razine-4-yl)propyl-1-phosphonate (10 mu M) abolished ictal discharges in the entorhinal cortex and reduced the duration of the interictal ev ents recorded in this area (n = 7). Interictal discharges originating. from CA3 continued to occur at a higher rate than in control during a pplication of this N-methyl-D-aspartate receptor antagonist. Our study confirms that the combined hippocampal-entorhinal slice preparation r epresents a suitable model for understanding the modalities of origin and propagation of epileptiform activity within the limbic system. In this in vitro preparation, the entorhinal cortex is the site of origin for ictal discharges. Moreover, the different types of epileptiform a ctivity induced by this muscarinic agonist have specific, structure-de pendent pharmacological profiles. These results are discussed in relat ion to those obtained in vivo.