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Here, conditional ablation of TAU in excitatory, but not inhibitory, neurons reduced epilepsy, sudden unexpected death in epilepsy, overactivation of the phosphoinositide 3-kinase\u2013AKT-mammalian target of rapamycin pathway, brain overgrowth (megalencephaly), and autism-like behaviors in a mouse model of Dravet syndrome, a severe epileptic encephalopathy of early childhood. Furthermore, treatment with a TAU-lowering antisense oligonucleotide, initiated on postnatal day 10, had similar therapeutic effects in this mouse model. Our findings suggest that excitatory neurons are the critical cell type in which TAU has to be reduced to counteract brain dysfunctions associated with Dravet syndrome and that overall cerebral TAU reduction could have similar benefits, even when initiated postnatally.<\/jats:p>","DOI":"10.1126\/scitranslmed.abm5527","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T17:53:41Z","timestamp":1651082021000},"source":"Crossref","is-referenced-by-count":55,"title":["TAU ablation in excitatory neurons and postnatal TAU knockdown reduce epilepsy, SUDEP, and autism behaviors in a Dravet syndrome model"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5307-8264","authenticated-orcid":true,"given":"Eric","family":"Shao","sequence":"first","affiliation":[{"name":"Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, 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