Gene reactivation diminishes delta-modulated high frequency oscillations during seizure-like events in Mecp2-deficient mice

Abstract

Genetically modified Mecp2-deficient mice provide a unique model of epilepsy associated with Rett syndrome. Examination of intracranial electroencephalogram (iEEG) recordings from mice lacking mecp2 function have revealed the presence of spontaneous epileptiform activity. To date the majority of these studies have focused on the low frequencies oscillations (LFOs), however, recent findings suggest there may be a link between high frequency oscillations (HFOs) and epileptogenesis. In this study the coupling of LFO phase to HFO amplitude was examined and identified modulation of HFO amplitude (400–600 Hz) by the phase of the high delta band (3–6 Hz) in male Mecp2-deficient mice diminishes after mecp2 gene reactivation therapy. These delta-HFO modulations were found to be strongly associated with long duration epileptiform discharges found primarily in the male non-rescue Mecp2-deficient mice. Differences in HFO interactions with high delta LFOs in male non-rescue and rescue mice could potentially be used as a biomarker for identifying the presence of seizure activity.