Dentate gyrus and hilus transection blocks seizure propagation and granule cell dispersion in a mouse model for mesial temporal lobe epilepsy

Authors

  • Johan Pallud,

    Corresponding author
    1. Service de Neurochirurgie, Centre Hospitalier Sainte-Anne, 75014 Paris
    2. Université René Descartes Paris V, 75014 Paris
    3. Centre de recherche “Grenoble—Institut des Neurosciences” U 836 Inserm-UJF-CEA-CHU, Equipe 9: Dynamique des Réseaux Synchrones épileptiques, bâtiment Edmond J. Safra, Domaine de la Merci, 38706 La Tronche cedex, France
    • Service de Neurochirurgie, Centre Hospitalier Sainte-Anne, 1, rue Cabanis, 75674 Paris Cedex 14, France
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  • Ute Häussler,

    1. Experimental Epilepsy, Neurocenter, University of Freiburg, Breisacherstrasse 64, 79106 Freiburg, Germany
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  • Mélanie Langlois,

    1. Centre de recherche “Grenoble—Institut des Neurosciences” U 836 Inserm-UJF-CEA-CHU, Equipe 9: Dynamique des Réseaux Synchrones épileptiques, bâtiment Edmond J. Safra, Domaine de la Merci, 38706 La Tronche cedex, France
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  • Sophie Hamelin,

    1. Centre de recherche “Grenoble—Institut des Neurosciences” U 836 Inserm-UJF-CEA-CHU, Equipe 9: Dynamique des Réseaux Synchrones épileptiques, bâtiment Edmond J. Safra, Domaine de la Merci, 38706 La Tronche cedex, France
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  • Bertrand Devaux,

    1. Service de Neurochirurgie, Centre Hospitalier Sainte-Anne, 75014 Paris
    2. Université René Descartes Paris V, 75014 Paris
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  • Colin Deransart,

    1. Centre de recherche “Grenoble—Institut des Neurosciences” U 836 Inserm-UJF-CEA-CHU, Equipe 9: Dynamique des Réseaux Synchrones épileptiques, bâtiment Edmond J. Safra, Domaine de la Merci, 38706 La Tronche cedex, France
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  • Antoine Depaulis

    1. Centre de recherche “Grenoble—Institut des Neurosciences” U 836 Inserm-UJF-CEA-CHU, Equipe 9: Dynamique des Réseaux Synchrones épileptiques, bâtiment Edmond J. Safra, Domaine de la Merci, 38706 La Tronche cedex, France
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Abstract

Epilepsy-associated changes of the anatomical organization of the dentate gyrus and hilus may play a critical role in the initiation and propagation of seizures in mesial temporal lobe epilepsy (MTLE). This study evaluated the role of longitudinal projections in the propagation of hippocampal paroxysmal discharges (HPD) in dorsal hippocampus by performing a selective transection in a mouse model for MTLE obtained by a single unilateral intrahippocampal injection of kainic acid (KA). Full transections of the dentate gyrus and hilus were performed in the transverse axis at 22 days after KA injection when spontaneous HPD were fully developed. They: (i) significantly reduced the occurrence of HPD; (ii) increased their duration at the KA injection site; (iii) abolished their spread along the longitudinal axis of the hippocampal formation and; (iv) limited granule cell dispersion (GCD) of the dentate gyrus posterior to the transection. These data suggest that: (i) longitudinal projections through the dentate gyrus and hilus are involved in HPD spread; (ii) distant hippocampal circuits participate in the generation and cessation of HPD and; (iii) GCD requires continuous HPD to develop, even when seizures are established. Our data reveal a critical role for longitudinal projections in the generation and spread of hippocampal seizures. © 2010 Wiley-Liss, Inc.

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