title: Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy.
abstract: The mechanisms involved in the transition to an epileptic seizure remain unclear. To examine them, we used tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability along with alkalinization or low Mg(2+). During the transition, distinct pre-ictal discharges emerged concurrently with interictal events. Intracranial recordings from the mesial temporal cortex of subjects with epilepsy revealed that similar discharges before seizures were restricted to seizure onset sites. In vitro, pre-ictal events spread faster and had larger amplitudes than interictal discharges and had a distinct initiation site. These events depended on glutamatergic mechanisms and were preceded by pyramidal cell firing, whereas interneuron firing preceded interictal events that depended on both glutamatergic and depolarizing GABAergic transmission. Once established, recurrence of these pre-ictal discharges triggered seizures. Thus, the subiculum supports seizure generation, and the transition to seizure involves an emergent glutamatergic population activity.
authors: Cortex and Epilepsy, l'Institut du Cerveau et de la Moelle Epinière, INSERM UMRS975, Centre National de la Recherche Scientifique UMR7225, Université Pierre et Marie Curie, Paris, France. gilles.huberfeld@upmc.fr
authors: Gilles
authors: G
authors: Huberfeld
authors: Liset
authors: L
authors: Menendez de la Prida
authors: Johan
authors: J
authors: Pallud
authors: Ivan
authors: I
authors: Cohen
authors: Michel
authors: M
authors: Le Van Quyen
authors: Claude
authors: C
authors: Adam
authors: Stéphane
authors: S
authors: Clemenceau
authors: Michel
authors: M
authors: Baulac
authors: Richard
authors: R
authors: Miles
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001703:Biophysics; D001931:Brain Mapping; D016001:Confidence Intervals; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000473:pathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D011189:Potassium Chloride; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D008274:Magnesium