title: Hippocampal hyperexcitability and specific epileptiform activity in a mouse model of Dravet syndrome.
abstract: OBJECTIVE
  Dravet syndrome (DS) is caused by dominant mutations of the SCN1A gene, encoding the NaV 1.1 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.
  
  
  METHODS
  We have studied heterozygous NaV 1.1 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Molecular and Cellular Pharmacology, CNRS UMR7275, University of Nice-Sophia Antipolis, Valbonne, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Liautard
authors.forename: Paolo
authors.initials: P
authors.lastname: Scalmani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Carriero
authors.forename: Marco
authors.initials: M
authors.lastname: de Curtis
authors.forename: Silvana
authors.initials: S
authors.lastname: Franceschetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Mantegazza
mesh_terms: D015761:4-Aminopyridine / Q000009:adverse effects; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006979:Hyperthermia, Induced / Q000009:adverse effects; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000172:deficiency / Q000235:genetics; D026902:Potassium Channel Blockers / Q000009:adverse effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D062550:NAV1.1 Voltage-Gated Sodium Channel; D026902:Potassium Channel Blockers; C568249:Scn1a protein, mouse; D015761:4-Aminopyridine; D007736:Kynurenic Acid; D001640:Bicuculline
keywords: Epilepsy; GABAergic inhibition; Hyperexcitability; Severe myoclonic epilepsy of infancy