title: Normotopic cortex is the major contributor to epilepsy in experimental double cortex.
abstract: OBJECTIVE
  Subcortical band heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats.
  
  
  METHODS
  Rats with SBH (Dcx-KD rats) were generated by knocking down the Dcx gene using shRNA vectors transfected into neocortical progenitors of rat embryos. Origin, spatial extent, and laminar profile of bicuculline-induced interictal-like activity on neocortical slices were analyzed by using extracellular recordings from 60-channel microelectrode arrays. Susceptibility to pentylenetetrazole-induced seizures was assessed by electrocorticography in head-restrained nonanesthetized rats.
  
  
  RESULTS
  We show that the band heterotopia does not constitute a primary origin for interictal-like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Furthermore, we report that most interictal-like discharges originating in the overlying cortex secondarily propagate to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx-KD rats to display seizures.
  
  
  CONCLUSIONS
  These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.
authors: Institut de Neurobiologie de la Méditerranée/Institut National de la Santé et de la Recherche Médicale U901, Marseille, France; Aix-Marseille University, Marseille, France.
authors: Ludovic Franck
authors: LF
authors: Petit
authors: Marion
authors: M
authors: Jalabert
authors: Emmanuelle
authors: E
authors: Buhler
authors: Arnaud
authors: A
authors: Malvache
authors: Angélique
authors: A
authors: Peret
authors: Yoann
authors: Y
authors: Chauvin
authors: Françoise
authors: F
authors: Watrin
authors: Alfonso
authors: A
authors: Represa
authors: Jean-Bernard
authors: JB
authors: Manent
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004569:Electroencephalography; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology*; D055785:Gene Knockdown Techniques; D008869:Microtubule-Associated Proteins / Q000235:genetics; D019579:Neocortex / Q000187:drug effects / Q000503:physiopathology*; D009415:Nerve Net / Q000002:abnormalities / Q000503:physiopathology; D009479:Neuropeptides / Q000235:genetics; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D055647:Rats, Transgenic; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology
chemical_list: D003292:Convulsants; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010433:Pentylenetetrazole; D001640:Bicuculline