Full-Length Original Research
Hippocampal hyperexcitability and specific epileptiform activity in a mouse model of Dravet syndrome
Version of Record online: 10 MAY 2013
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
Volume 54, Issue 7, pages 1251–1261, July 2013
How to Cite
Liautard, C., Scalmani, P., Carriero, G., de Curtis, M., Franceschetti, S. and Mantegazza, M. (2013), Hippocampal hyperexcitability and specific epileptiform activity in a mouse model of Dravet syndrome. Epilepsia, 54: 1251–1261. doi: 10.1111/epi.12213
- Issue online: 1 JUL 2013
- Version of Record online: 10 MAY 2013
- Manuscript Accepted: 2 APR 2013
- LabEx ICST, Mariani Foundation. Grant Number: R-12-94
- Italian Ministry of Health. Grant Number: GR-2007-657156
- European Integrated Project EPICURE. Grant Number: EFP6-037315
- Fondation pour la Recherche Medicale
- ERANET NEURON “2P-imaging”
- Italian Telethon. Grant Number: GGP10138A
- GABAergic inhibition;
- Severe myoclonic epilepsy of infancy
Dravet syndrome (DS) is caused by dominant mutations of the SCN1A gene, encoding the NaV1.1 sodium channel α subunit. Gene targeted mouse models of DS mutations replicate patients' phenotype and show reduced γ-aminobutyric acid (GABA)ergic inhibition. However, little is known on the properties of network hyperexcitability and on properties of seizure generation in these models. In fact, seizures have been studied thus far with surface electroencephalography (EEG), which did not show if specific brain regions are particularly involved. We have investigated hyperexcitability and epileptiform activities generated in neuronal networks of a mouse model of DS.
We have studied heterozygous NaV1.1 knock-out mice performing field potential recordings in combined hippocampal/cortical slices in vitro and video/depth electrode intracerebral recordings in vivo during hyperthermia-induced seizures.
In slices, we have disclosed specific signs of hyperexcitability of hippocampal circuits in both the pre-epileptic and epileptic periods, and a specific epileptiform activity was generated in the hippocampus upon application of the convulsant 4-aminopyridine in the epileptic period. During in vivo hyperthermia-induced seizures, we have observed selective hippocampal activity in early preictal phases and pronounced hippocampal activity in the ictal phase.
We have identified specific epileptiform activities and signs of network hyperexcitability, and disclosed the important role of the hippocampus in seizure generation in this model. These activities may be potentially used as targets for screenings of antiepileptic approaches.