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We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.<\/jats:p>","DOI":"10.7554\/elife.48648","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T08:00:49Z","timestamp":1569225649000},"source":"Crossref","is-referenced-by-count":22,"title":["The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero"],"prefix":"10.7554","volume":"8","author":[{"given":"Alexander GJ","family":"Skorput","sequence":"first","affiliation":[{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States"},{"name":"Department of Neuroscience, School of Medicine, University of Minnesota Twin Cities, Minneapolis, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-7144","authenticated-orcid":true,"given":"Stephanie 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