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Here, we investigated the time course of maturation of neuronal GABAergic signaling in the <jats:italic>Scn1b<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Scn1a<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mouse models of DS. We found that GABAergic signaling remains immature in both DS models, with a depolarized reversal potential for GABA<jats:sub>A<\/jats:sub>-evoked currents compared to wildtype in the third postnatal week. Treatment of <jats:italic>Scn1b<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with bumetanide resulted in a delay in SUDEP onset compared to controls in a subset of mice, without prevention of seizure activity or amelioration of failure to thrive. We propose that delayed maturation of GABAergic signaling may contribute to epileptogenesis in <jats:italic>SCN1B<\/jats:italic>- and <jats:italic>SCN1A<\/jats:italic>-linked DS. Thus, targeting the polarity of GABAergic signaling in brain may be an effective therapeutic strategy to reduce SUDEP risk in DS.<\/jats:p>","DOI":"10.1038\/s41598-019-42191-0","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T10:14:19Z","timestamp":1555496059000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Delayed maturation of GABAergic signaling in the Scn1a and Scn1b mouse models of Dravet Syndrome"],"prefix":"10.1038","volume":"9","author":[{"given":"Yukun","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"O\u2019Malley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Smaldino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra A.","family":"Bouza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Hull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9479-6729","authenticated-orcid":false,"given":"Lori L.","family":"Isom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"issue":"Suppl 2","key":"42191_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1528-1167.2011.02994.x","volume":"52","author":"C Dravet","year":"2011","unstructured":"Dravet, C. 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