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To address this gap, we used an optogenetic approach to activate and inactivate neurons in the dorsal striatum of rats submitted to the gamma-butyrolactone (GBL) model of absence epilepsy, amygdala kindling model of temporal lobe epilepsy, and pilocarpine-induced Status Epilepticus (SE). Open-loop (continuous light delivery) optogenetic activation of dorsal striatal neurons robustly suppressed seizures in all models. By contrast, open-loop optogenetic silencing increased absence seizure expression and facilitated SE onset but had no effect on kindled seizures. In the GBL model, we also tested the effects of closed-loop modulation (light delivery in response to seizure detection). Closed-loop activation reduced duration of spike-wave discharges (SWDs), while closed-loop inhibition increased SWD duration. These results demonstrated previously unrecognized antiabsence effects associated with striatal neuromodulation. These findings demonstrate a robust, bidirectional role of the dorsal striatum in the control of multiple seizure types, suggesting that the striatum is a site that can exert broad-spectrum control of seizures.<\/jats:p>","DOI":"10.1073\/pnas.2419178122","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T15:01:18Z","timestamp":1743433278000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":15,"title":["Optogenetic stimulation of the dorsal striatum bidirectionally controls seizures"],"prefix":"10.1073","volume":"122","author":[{"given":"Safwan K.","family":"Hyder","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-9495","authenticated-orcid":false,"given":"Willian","family":"Lazarini-Lopes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7538-2645","authenticated-orcid":false,"given":"Jonathan","family":"Toib","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Sukharev","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Neuroscience, Georgetown University","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-060X","authenticated-orcid":false,"given":"Patrick A.","family":"Forcelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University","place":["Washington"]},{"name":"Interdisciplinary Program in Neuroscience, Georgetown University","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1273163","DOI":"10.3389\/fepid.2023.1273163","article-title":"Editorial: Epidemiology of epilepsy and seizures","volume":"3","author":"Chen Z.","year":"2023","unstructured":"Z. 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