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Selective inhibition of subicular pyramidal neurons by optogenetics or chemogenetics reversed phenytoin resistance, whereas selective activation of subicular pyramidal neurons induced phenytoin resistance. Moreover, long\u2010term low\u2010frequency stimulation at the subiculum, which is clinically feasible, significantly inhibited the subicular pyramidal neurons and reversed phenytoin resistance. Furthermore, in vitro electrophysiology revealed that off\u2010target use of phenytoin on sodium channels of subicular pyramidal neurons was involved in the phenytoin resistance, and clinical neuroimaging data suggested the volume of the subiculum in drug\u2010resistant patients was related to the usage of sodium channel inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These results highlight that the subicular pyramidal neurons may be a key switch control of drug\u2010resistant epilepsy and represent a new potential target for precise treatments. ANN NEUROL 2019;86:626\u2013640<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25554","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T12:48:23Z","timestamp":1563972503000},"page":"626-640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Subicular pyramidal neurons gate drug resistance in temporal lobe epilepsy"],"prefix":"10.1002","volume":"86","author":[{"given":"Cenglin","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Key Laboratory of Medical Neurobiology of National Health Commission and Chinese Academy of Medical Sciences, College of Pharmaceutical Sciences Zhejiang University  Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Key Laboratory of Medical 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