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J Neurophysiol (June 24, 2009). doi:10.1152/jn.90795.2008
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90795.2008v1
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Submitted on July 21, 2008
Revised on June 15, 2009
Accepted on June 15, 2009

The slow oscillation state facilitates epileptiform events in the hippocampus

Farhang Nazer1 and Clayton T Dickson1*

1 University of Alberta

* To whom correspondence should be addressed. E-mail: clayton.dickson{at}ualberta.ca.

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 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 urethane anesthesia: the slow oscillation (SO). This activity is characterized by a high amplitude ~1Hz signal, high synchrony within the hippocampus, and a dynamic coordination with neocortical SO. In order 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 urethane-anaesthetized 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. Lastly, 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.







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