Characterization of HFOs in short and long duration discharges recorded from in-vivo MeCP2-deficient mice

Abstract

Mutations in the X-linked gene encoding methyl CpG-binding protein 2 (MeCP2) have been linked to a neurodevelopmental disorder known as Rett syndrome. The disorder is associated with a number of symptoms, of which epileptic seizures are common. In this study we examined the presence of high frequency oscillations (HFOs) and their interactions with low frequency oscillations (LFOs) during epileptiform-like discharges using intracranial electroencephalogram (iEEG) recordings from male and female Mecp2-deficient mice. The study compared differences in mean HFO power levels normalized to baseline along with LFO-HFO modulation observed in short and long duration discharges. Short duration discharges, common to both male and female Mecp2-deficient mice, showed a decrease in mean HFO power levels compared to baseline levels. During the short duration discharges the theta (7-9 Hz) LFOs were found to modulate fast ripple (350-500 Hz) HFOs predominantly in the female Mecp2-deficient mice. Long duration discharges, predominantly observed in male Mecp2-deficient mice, were found to have elevated mean power levels in the ripple (80-200 Hz) and fast ripple (350-500 Hz) frequency ranges when compared to baseline. During the long duration discharges a lower frequency range theta LFO (4-6 Hz) modulated both the ripple (80-200 Hz) and fast ripple (350-500 Hz) HFOs. These findings suggest that the long duration discharges observed in male Mecp2-deficient mice share biomarkers indicative of seizure-like activity.