Slow Oscillation State Facilitates Epileptiform Events in the Hippocampus

Abstract

In mesial temporal lobe (MTL) epilepsy, which typically involves the hippocampus (HPC), epileptiform events are enhanced during slow wave sleep (SWS). It remains unclear how and why the electroencephalographic (EEG) states that constitute SWS might predispose the HPC to this type of pathological activity. Recently our laboratory has described a novel state of deactivated hippocampal EEG activity that occurs during both SWS and urethan anesthesia: the slow oscillation (SO). This activity is characterized by a high-amplitude approximately 1-Hz signal, high synchrony within the hippocampus, and a dynamic coordination with neocortical SO. To assess how this activity state might influence epileptiform discharges, we studied the properties of stimulation-evoked and spontaneous epileptiform events elicited in the HPC of urethan-anesthetized rats. We compared those elicited during the SO to those occurring during the theta rhythm. The average duration but not the amplitude of evoked afterdischarges (ADs) was consistently larger during the SO. In addition, spontaneous epileptiform events were more frequent and of higher amplitude during the SO. Last, the bilateral propagation of both ADs and spontaneous events in the hippocampus was enhanced during the SO. These results imply that the threshold for the generation and propagation of epileptiform activity in the hippocampus is lowered during the SO and that this state may be a seed for the initiation, maintenance, and generalization of MTL epilepsy. Further examination of the pathophysiology of sleep-epilepsy interactions in the HPC will be of benefit for an understanding of the mechanisms, prognosis, and therapy for this form of epilepsy.