Abstracts

Rationale: It has been established that cooling can terminate spontaneous epileptiform discharges in animal models of epilepsy. Further, we have shown that rapid cooling can terminate epileptiform discharges within a few seconds. However, the mechanism of this effect has not been clearly established. We have hypothesized that interruption of synchrony in the hippocampal network may contribute to the effects of cooling. Here we report the results of simultaneous intra- and extracellular recordings from hippocampal neurons in acute slices. Methods: Simultaneous dual recording using whole-cell patch clamp, cell attached and field recordings were carried out from mouse hippocampal pyramidal cells and interneurons. The slices were perfused with 50 μM 4-aminopyridine at an initial temperature of 30-34οC. Cooling was induced at a rate of 0.1-2οC/s by switching to cold aCSF and warming was achieved via a heater at a slower rate. Grounding was placed in an adjacent chamber to minimize temperature dependent effects on junction potential. Results: Baseline recording showed a significant degree of synchrony and coupling between the pyramidal cells and interneurons in their vicinity. Rapid cooling resulted in suppression of the spontaneous discharges in the CA1 and CA3 pyramidal cells while in the interneurons it only decreased the activity without complete cessation. These results were location dependent. In the hippocampal network, rapid cooling also interrupted the synchrony between the pyramidal cells themselves, and pyramidal cells and interneurons. The effects of cooling on synchrony of the spontaneous discharges was sometimes observed several minutes after re-warming. Conclusions: Disturbing the normal synchrony between different cell types in the hippocampus, in particular between pyramidal cells and interneurons may contribute to the effects of cooling in slice models of epilepsy.