{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:17:56Z","timestamp":1790839076412,"version":"4.1.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-15-IDEX-01"],"award-info":[{"award-number":["ANR-15-IDEX-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-11-LABX-0015-01"],"award-info":[{"award-number":["ANR-11-LABX-0015-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ville de Nice, France","award":["Aides Individuelles Jeunes Chercheurs"],"award-info":[{"award-number":["Aides Individuelles Jeunes Chercheurs"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,6,4]]},"abstract":"<jats:p>\n                    Epilepsies have numerous specific mechanisms. The understanding of neural dynamics leading to seizures is important for disclosing pathological mechanisms and developing therapeutic approaches. We investigated electrographic activities and neural dynamics leading to convulsive seizures in patients and mouse models of Dravet syndrome (DS), a developmental and epileptic encephalopathy in which hypoexcitability of GABAergic neurons is considered to be the main dysfunction. We analyzed EEGs from DS patients carrying a\n                    <jats:italic>SCN1A<\/jats:italic>\n                    pathogenic variant, as well as epidural electrocorticograms, hippocampal local field potentials, and hippocampal single-unit neuronal activities in\n                    <jats:italic>Scn1a<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Scn1a<\/jats:italic>\n                    <jats:sup>RH\/+<\/jats:sup>\n                    DS mice. Strikingly, most seizures had low-voltage-fast onset in both patients and mice, which is thought to be generated by hyperactivity of GABAergic interneurons, the opposite of the main pathological mechanism of DS. Analyzing single-unit recordings, we observed that temporal disorganization of the firing of putative interneurons in the period immediately before the seizure (preictal) precedes the increase of their activity at seizure onset, together with the entire neuronal network. Moreover, we found early signatures of the preictal period in the spectral features of hippocampal and cortical field potential of\n                    <jats:italic>Scn1a<\/jats:italic>\n                    mice and of patients\u2019 EEG, which are consistent with the dysfunctions that we observed in single neurons and that allowed seizure prediction. Therefore, the perturbed preictal activity of interneurons leads to their hyperactivity at the onset of generalized seizures, which have low-voltage-fast features that are similar to those observed in other epilepsies and are triggered by hyperactivity of GABAergic neurons. Preictal spectral features may be used as predictive seizure biomarkers.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2316364121","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T12:17:16Z","timestamp":1716985036000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Preictal dysfunctions of inhibitory interneurons paradoxically lead to their rebound hyperactivity and to low-voltage-fast onset seizures in Dravet syndrome"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5718-4002","authenticated-orcid":false,"given":"Fabrizio","family":"Capitano","sequence":"first","affiliation":[{"name":"University Cote d\u2019Azur, Institute of Molecular and Cellular Pharmacology, Valbonne-Sophia Antipolis 06560, France"},{"name":"CNRS UMR 7275, Valbonne-Sophia Antipolis 06560, France"},{"name":"Inserm U1323, Valbonne-Sophia Antipolis 06650, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5944-2204","authenticated-orcid":false,"given":"Mathieu","family":"Kuchenbuch","sequence":"additional","affiliation":[{"name":"Reference Centre for Rare Epilepsies, Member of European Reference Network EpiCARE, Department of Pediatric Neurology, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris, Paris 75015, France"},{"name":"Laboratory of Translational Research for Neurological Disorders, Inserm UMR 1163, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, Paris 75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lavigne","sequence":"additional","affiliation":[{"name":"University Cote d\u2019Azur, Institute of Molecular and Cellular Pharmacology, Valbonne-Sophia Antipolis 06560, France"},{"name":"CNRS UMR 7275, Valbonne-Sophia Antipolis 06560, France"},{"name":"Inserm U1323, Valbonne-Sophia Antipolis 06650, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0859-4059","authenticated-orcid":false,"given":"Hava","family":"Chaptoukaev","sequence":"additional","affiliation":[{"name":"EURECOM, Biot-Sophia Antipolis 06410, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-766X","authenticated-orcid":false,"given":"Maria A.","family":"Zuluaga","sequence":"additional","affiliation":[{"name":"EURECOM, Biot-Sophia Antipolis 06410, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0521-2881","authenticated-orcid":false,"given":"Marco","family":"Lorenzi","sequence":"additional","affiliation":[{"name":"University Cote d\u2019Azur, Institute of Molecular and Cellular Pharmacology, Valbonne-Sophia Antipolis 06560, France"},{"name":"Epione Research team, Inria Center of Universit\u00e9 C\u00f4te d\u2019Azur, Biot-Sophia Antipolis 06410, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Nabbout","sequence":"additional","affiliation":[{"name":"Reference Centre for Rare Epilepsies, Member of European Reference Network EpiCARE, Department of Pediatric Neurology, H\u00f4pital Necker-Enfants Malades, Assistance Publique H\u00f4pitaux de Paris, Paris 75015, France"},{"name":"Laboratory of Translational Research for Neurological Disorders, Inserm UMR 1163, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, Paris 75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1070-7929","authenticated-orcid":false,"given":"Massimo","family":"Mantegazza","sequence":"additional","affiliation":[{"name":"University Cote d\u2019Azur, Institute of Molecular and Cellular Pharmacology, Valbonne-Sophia Antipolis 06560, France"},{"name":"CNRS UMR 7275, Valbonne-Sophia Antipolis 06560, France"},{"name":"Inserm U1323, Valbonne-Sophia Antipolis 06650, 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Mantegazza Original data for: Preictal dysfunctions of inhibitory interneurons paradoxically lead to their rebound hyperactivity and to low-voltage-fast onset seizures in Dravet syndrome. Zenodo. https:\/\/zenodo.org\/records\/11211735. Deposited 17 May 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2316364121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T12:18:21Z","timestamp":1716985101000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2316364121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,29]]},"references-count":58,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,6,4]]}},"alternative-id":["10.1073\/pnas.2316364121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2316364121","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.09.20.558646","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,29]]},"assertion":[{"value":"2023-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2316364121"}}