{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:53:10Z","timestamp":1791028390975,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The voltage\u2010gated sodium channel Nav1.1, encoded by\n                      <jats:italic>Scn1a<\/jats:italic>\n                      , is essential for \u03b3\u2010aminobutyric acid (GABA)ergic function, and its alteration is associated with neurological disorders such as Dravet syndrome and Alzheimer's disease. We previously demonstrated that local Nav1.1 dysfunction in the medial prefrontal cortex (mPFC) during adolescence causes epilepsy, cognitive deficits, and depressive\u2010like behaviors. Here, to investigate putative developmental differences, we analyzed whether Nav1.1 dysfunction in the adult mPFC produces comparable phenotypic outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Nav1.1 dysfunction was selectively induced in the adult mPFC via conditional expression of a mutant human\n                      <jats:italic>SCN1A<\/jats:italic>\n                      variant. We then analyzed PFC\u2010related cognitive tasks and depressive\u2010like behaviors; epileptic and oscillatory activity using in\u00a0vivo electroencephalography (EEG) recordings; and ex\u00a0vivo synaptic plasticity in mPFC circuits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:italic>Results<\/jats:italic>\n                    <\/jats:title>\n                    <jats:p>As observed after adolescent Nav1.1 dysfunction, adult manipulation induced epileptic activity and depressive\u2010like phenotypes. However, mPFC\u2010dependent cognitive functions remained intact, unlike adolescent mice, which showed impaired working memory and fear extinction. Electrophysiological recordings revealed distinct mPFC oscillatory patterns. Adult Nav1.1 dysfunction reduced sleep\u2010related delta mPFC power and dorsal hippocampus (dHPC)\u2013mPFC coherence, mimicking adolescent patterns. In contrast, no alteration in mPFC oscillatory activity was observed during wakefulness, differing from adolescent mice. IN addition, synaptic plasticity analyses showed that adolescent\u2014but not adult\u2014Nav1.1 dysfunction impaired long\u2010term potentiation (LTP) at cortical L2\/3\u2013L2\/3 prelimbic synapses. Moreover, LTP was sensitive to Nav1.1 pharmacological activation only in adolescent mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These findings reveal a developmental role for Nav1.1 activity in mPFC plasticity and cognition, whereas in adulthood, it remains critical for regulating network stability and depressive\u2010like behaviors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70484","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:05:14Z","timestamp":1791025514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Scn1a<\/i>\n                    \u2010mediated developmental regulation of prefrontal cortex plasticity and cognition"],"prefix":"10.1002","author":[{"given":"Maurizio S.","family":"Riga","sequence":"first","affiliation":[{"name":"Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER) CSIC\u2010JA\u2010US\u2010UPO  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"P\u00e9rez\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER) CSIC\u2010JA\u2010US\u2010UPO  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuniesky","family":"Andrade\u2010Talavera","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cell Biology University Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0621-650X","authenticated-orcid":false,"given":"Benito","family":"Dom\u00ednguez\u2010Velasco","sequence":"additional","affiliation":[{"name":"Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER) CSIC\u2010JA\u2010US\u2010UPO  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rodr\u00edguez\u2010Moreno","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cell Biology University Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0655-8289","authenticated-orcid":false,"given":"Manuel","family":"\u00c1lvarez\u2010Dolado","sequence":"additional","affiliation":[{"name":"Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER) 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