Absence-like Seizures, Cortical Oscillations Abnormalities and Decreased Anxiety-like Behavior in Wistar Audiogenic Rats with Cortical Microgyria

Abstract

Wistar Audiogenic Rats (WAR) is an inbred rodent strain susceptible to acute auditory stimulation-induced seizures. However, spontaneous epileptic seizures (SES) and their associated electroencephalogram (EEG) abnormalities have not been reported in WAR kindled animals. The same is true for naïve WARs (without sound-induced seizures). An approach to increment epileptogenesis and SES is to use a second insult to be added to the genetic background. Here, we used adult naïve WARs with microgyria induced by neonatal cortical freeze-lesion (FL) to evaluate the occurrence of SES and the modification in cortical oscillation patterns and behavior. The neonatal cortical FL was performed in Wistar and naïve WARs (Wis-FL and WAR-FL). Sham animals were used as controls (Wistar-S and WAR-S). Video-EEG recordings and behavioral tasks were performed during adulthood. Surprisingly, spike-waive discharges (SWD) events associated with behavior arrest were detected in WAR-S rats. Those events increased in duration and number in WAR-FL animals. The EEG quantitative analysis showed decreased power of cortical delta, theta and beta oscillations in WAR-S, decreased power of cortical fast gamma (FG) oscillations in WARs, independent of microgyria, and decreased interhemispheric synchrony for delta and FG with stronger coupling in delta and theta-FG oscillations in FL animals. The WARs, regardless of microgyria, had reduced locomotor activity, but only WAR-FL animals had reduced anxiety-like behavior. Microgyria in naïve WARs intensified SWD events associated with behavior arrest that could reflect absence-like seizures and abnormal cortical oscillations, and reduced anxiety-like behavior indicating that WAR-FL could be a reliable model to study epileptogenesis.