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Keywords:

  • Epilepsy;
  • Hippocampus;
  • Cooling;
  • Hypothermia;
  • Synchronization

Summary:  Purpose: We sought to determine whether cooling brain tissue from 34 to 21°C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission.

Methods: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450–500 μm) from Sprague–Dawley male rats, maintained in an air–fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34°C, reduced to 21°C within 20 min.

Results: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a γ-aminobutyric acid (GABA)A-receptor antagonist. Cooling from 34 to 21°C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse–evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner.

Conclusions: Tetany-induced neuronal network synchronization by GABAA-sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity.