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.

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.

• Authors: Ludovic Franck Petit, Marion Jalabert, Emmanuelle Buhler, Arnaud Malvache, Angélique Peret, Yoann Chauvin, Françoise Watrin, Alfonso Represa, Jean-Bernard Manent
• Journal: Annals of neurology (Ann Neurol) Vol. 76 Issue 3 Pg. 428-42 (Sep 2014) ISSN: 1531-8249 [Electronic] United States
• PMID: 25074818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Neurological Association.

Chemical References

• Convulsants
• Dcx protein, rat
• Doublecortin Domain Proteins
• Doublecortin Protein
• Microtubule-Associated Proteins
• Neuropeptides
• Pentylenetetrazole
• Bicuculline

Topics

• Animals
• Bicuculline (pharmacology)
• Cerebral Cortex (drug effects, physiopathology)
• Classical Lissencephalies and Subcortical Band Heterotopias (complications, pathology, physiopathology)
• Convulsants (pharmacology)
• Disease Models, Animal
• Doublecortin Domain Proteins
• Doublecortin Protein
• Electroencephalography
• Electrophysiological Phenomena (drug effects, physiology)
• Epilepsy (chemically induced, etiology, physiopathology)
• Gene Knockdown Techniques
• Microtubule-Associated Proteins (genetics)
• Neocortex (drug effects, physiopathology)
• Nerve Net (abnormalities, physiopathology)
• Neuropeptides (genetics)
• Pentylenetetrazole (pharmacology)
• Rats
• Rats, Transgenic
• Seizures (chemically induced, physiopathology)
• Somatosensory Cortex (drug effects, physiopathology)