Reduction of spike generation frequency by cooling in brain slices from rats and from patients with epilepsy

Abstract

This study aimed to understand the mechanism by which brain cooling terminates epileptic discharge. Cortical slices were prepared from rat brains (n = 19) and samples from patients with intractable epilepsy that had undergone temporal lobectomy (n = 7). We performed whole cell current clamp recordings at approximately physiological brain temperature (35℃) and at cooler temperatures (25℃ and 15℃). The firing threshold in human neurons was lower at 25℃ (−32.6 mV) than at 35℃ (−27.0 mV). The resting potential and spike frequency were similar at 25℃ and 35℃. Cooling from 25℃ to 15℃ did not change the firing threshold, but the resting potential increased from −65.5 to −54.0 mV and the waveform broadened from 1.85 to 6.55 ms, due to delayed repolarization. These changes enhanced the initial spike appearance and reduced spike frequency; moreover, spike frequency was insensitive to increased levels of current injections. Similar results were obtained in rat brain studies. We concluded that the reduction in spike frequency at 15℃, due to delayed repolarization, might be a key mechanism by which brain cooling terminates epileptic discharge. On the other hand, spike frequency was not influenced by the reduced firing threshold or the elevated resting potential caused by cooling.