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Summary   Objective  Malformations of cortical development are common causes of intellectual disability and epilepsy, yet there is a crucial lack of relevant preclinical models associating seizures and cortical malformations. Here, we describe a novel rat model with bilateral subcortical band heterotopia ( SBH ) and examine whether this model develops spontaneous epileptic seizures.    Methods  To generate bilateral  SBH  in rats, we combined  RNA i‐mediated knockdown of  Dcx  and in utero electroporation with a tripolar electrode configuration enabling simultaneous transfection of the two brain hemispheres. To determine whether bilateral  SBH  leads to epileptiform activity, rats of various ages were implanted for telemetric electrocorticographic recordings and histopathological examination was carried out at the end of the recording sessions.    Results  By 2 months, rats with bilateral  SBH  showed nonconvulsive spontaneous seizures consisting of spike‐and‐wave discharges ( SWD s) with dominant frequencies in the alpha and theta bands and secondarily in higher‐frequency bands.  SWD s occurred during both the dark and the light period, but were more frequent during quiet awake state than during sleep. Also,  SWD s were more frequent and lasted longer at older ages. No sex differences were found. Although frequencies and durations of  SWD s were found to be uncorrelated with the size of  SBH ,  SWD s were initiated in some occasions from brain hemispheres comprising a larger  SBH . Lastly,  SWD s exhibited absence‐like pharmacological properties, being temporarily alleviated by ethosuximide administration.    Significance  This novel model of bilateral  SBH  with spontaneous epilepsy may potentially provide valuable new insights into causality between cortical malformations and seizures, and help translational research aiming at designing novel treatment strategies for epilepsy.

Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia