Short-Duration Epileptic Discharges Show a Distinct Phase Preference During Ongoing Hippocampal Slow Oscillations

Abstract

Non-REM (slow-wave) sleep has been shown to facilitate temporal lobe epileptiform events, whereas REM sleep seems more restrictive. This state-dependent modulation may be the result of the enhancement of excitatory synaptic transmission and/or the degree of network synchronization expressed within the hippocampus of the temporal lobe. The slow oscillation (SO), a ∼1 Hz oscillatory pattern expressed during non-REM sleep and urethane anesthesia, has been recently shown to facilitate the generation, maintenance, and propagation of stimulus-evoked epileptiform activity in the hippocampus. To further address the state-dependent modulation of epileptic activity during the SO, we studied the properties of short-duration interictal-like activity generated by focal application of penicillin in the hippocampus of urethane-anesthetized rats. Epileptiform spikes were larger but only slightly more prevalent during the SO as opposed to the theta (REM-like) state. More notably, however, epileptic spikes had a significant tendency to occur just following the peak negativity of ongoing SO cycles. Because of the known phase-dependent changes in 1) synaptic excitability (just following the positive peak of the SO) and 2) network synchronization (during the negative peak of the SO), these results suggest that it is the synchrony and not the changes in synaptic excitability that lead to the facilitation of epileptiform activity during sleep-like slow wave states.