Normotopic cortex is the major contributor to epilepsy in experimental double cortex. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Annals of Neurology Année : 2014

Normotopic cortex is the major contributor to epilepsy in experimental double cortex.

Résumé

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. INTERPRETATION: 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. Ann Neurol 2014.
Fichier sous embargo
Fichier sous embargo
Fichier sous embargo
Fichier sous embargo
Fichier sous embargo
Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée
Fichier sous embargo
Date de visibilité indéterminée
Fichier sous embargo
Date de visibilité indéterminée
Fichier sous embargo
Date de visibilité indéterminée
Fichier sous embargo
Date de visibilité indéterminée
Fichier sous embargo
Date de visibilité indéterminée
Loading...

Dates et versions

inserm-01059741 , version 1 (01-09-2014)

Identifiants

Citer

Ludovic Franck Petit, Marion Jalabert, Emmanuelle Buhler, Arnaud Malvache, Angélique Peret, et al.. Normotopic cortex is the major contributor to epilepsy in experimental double cortex.: Origin of epileptic activity in experimental SBH. Annals of Neurology, 2014, 76 (3), pp.428-42. ⟨10.1002/ana.24237⟩. ⟨inserm-01059741⟩

Collections

INSERM UNIV-AMU
151 Consultations
2 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More