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 Mg2+. 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.
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Acknowledgements
We wish to thank M. Noulhiane for her help with imaging and statistics, M.-L. Tanguy for help with statistical analysis, E. Eugène for his technical assistance, M. Valderrama for software assistance and L. Wittner for participating in initial recordings. We gratefully acknowledge financial support from INSERM, the CNRS, the AP-HP, the Fédération pour la Recherche Médicale, the Fédération pour la Recherche sur le Cerveau, the Agence Nationale de la Recherche, the European Community (EPICURE, LSH-037315), Spain-France Joint Action (HF2006-0082), the Spanish National Research Council (Consejo Superior de Investigaciones Científicas 200720I023) and the Spanish Ministry of Innovation and Science (BFU2006-10584-BFI and BFU2009-07989).
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G.H., L.M.d.l.P. and R.M. designed the study. G.H., L.M.d.l.P. and R.M. performed the in vitro experiments. G.H., S.C., J.P., C.A. and M.B. performed the in vivo work and analysis. G.H., L.M.d.l.P., J.P., I.C., M.L.V.Q. and R.M. contributed to data analysis. G.H. and R.M. wrote the paper.
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Huberfeld, G., Menendez de la Prida, L., Pallud, J. et al. Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy. Nat Neurosci 14, 627–634 (2011). https://doi.org/10.1038/nn.2790
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DOI: https://doi.org/10.1038/nn.2790
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