Abstracts

Rationale: Rodent in vivo EEG is valuable for preclinical drug discovery. Healthy rodents without a genetic or acquired predisposition toward epilepsy have occasional epileptiform discharges on EEG that resemble the spikes and sharp waves attributed to epilepsy. This phenomenon has been described in rats where such discharges are termed high-voltage rhythmic spikes. Though these discharges have been described and investigated in wild-type (WT) rats, little work has been done to characterize similar activity in mice. In this study, we aim to describe the epileptiform activity in 24-hour EEG recordings of WT mice. Our goal is to characterize these discharges to improve our understanding of the normal background features of mouse EEG, so as to better distinguish between pathological and normal EEG activity in mouse epilepsy models. Methods: Male C57 WT mice (n=40, 1-2mo) that served as littermate WT controls for separate experiments involving mice carrying Fmr1, Pten, Shank3b, Gabr3b, and Cntnap2 mutations, and an additional group of naïve C57 were implanted with wireless EEG transmitters for long-term monitoring. 24-hours EEG record per mouse was analyzed by visual inspection wherein two independent reviewers manually marked single electrographic spikes and spike trains (= 3 continuous spikes) based on individual spike characteristics such as amplitude, duration, and frequency. Concomitant video playback was used to differentiate spiking events from electrical and mechanical artifact.  Results: Epileptiform spikes were detected in 100% of the recorded WT mice with 188.6 ± 97.1 spikes per mouse and about 7.9 ± 4.1 spikes per hour. Spike trains were recorded in 90% mice with an average 3.6 ± 1.2 spikes per spike train lasting 0.4 ± 0.1 seconds per train. The spiking activity was significantly more frequent (spikes, p<0.0001; spike trains p=0.004) during the day than in night, which was inversely correlated to the animal's locomotor activity and alertness levels during these periods.  Conclusions: Electrographic single spikes are universal to all mice and trains of spikes are also very commonly found in WT mouse EEG. These discharges may be indicative of epileptiform activity or perhaps are elements of normal rodent electrophysiological background EEG activity. Funding: Preclinical Autism Consortium for Therapeutics (PACT)Boston Children's Hospital Translational Research Program (BCH-TRP)