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Yet, therapeutic options remain limited by our incomplete understanding of what neural circuits underly the condition. Although cerebellar nuclei neurons are implicated in the origin of baseline dystonic symptoms, it is unclear whether their activity drives dystonic crisis. To explore this role, we found that cerebellar abnormalities and neural inhibition were recurring targets in patients with dystonic crisis, implicating cerebellar inhibitory neurons in its development. We devised a mouse genetics approach to test whether inhibitory cerebellar nuclei neurons (iCNNs) induce dystonic crisis. Directional optogenetic modulation of iCNNs induced dystonic crises on-demand and alleviated spontaneous crises in mice that mimic spontaneous dystonic crises. To investigate whether iCNNs interact with other motor areas during dystonic crisis, we identified monosynaptic iCNN projections to the centrolateral nucleus of the thalamus (CL). Deep brain stimulation of the CL alleviated dystonic crises induced by iCNN photoactivation. Our data uncover a cell type-specific cerebellar origin of dystonic crisis and highlight its therapeutic potential.<\/jats:p>","DOI":"10.64898\/2026.04.01.715774","type":"posted-content","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T21:00:19Z","timestamp":1775250019000},"source":"Crossref","is-referenced-by-count":0,"title":["Human and mouse cerebellar inhibitory circuits in dystonic crisis and their modulation with therapeutic stimulation"],"prefix":"10.64898","author":[{"given":"Alejandro G.","family":"Rey Hipolito","sequence":"first","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Cerebellum Science Center, Texas Children\u2019s Hospital, Houston, Texas, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Dew","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Cerebellum Science Center, Texas Children\u2019s Hospital, Houston, Texas, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4235-2269","authenticated-orcid":false,"given":"Jason S.","family":"Gill","sequence":"additional","affiliation":[{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine, Houston, Texas, USA"},{"name":"Cerebellum Science Center, Texas Children\u2019s Hospital, Houston, Texas, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janelle E.","family":"Allen","sequence":"additional","affiliation":[{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine, Houston, Texas, USA"},{"name":"Cerebellum Science Center, Texas Children\u2019s Hospital, Houston, Texas, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karissa A.","family":"Chesky","sequence":"additional","affiliation":[{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine, Houston, Texas, USA"},{"name":"Cerebellum Science Center, Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam","family":"Hull","sequence":"additional","affiliation":[{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics Baylor College of Medicine, Houston, Texas, USA"},{"name":"Cerebellum Science Center, Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-6190","authenticated-orcid":false,"given":"Roy V.","family":"Sillitoe","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA"},{"name":"Cerebellum Science Center, Texas Children\u2019s Hospital, Houston, Texas, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026040701001294000_2026.04.01.715774v1.1","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1002\/mds.30220","article-title":"Definition and classification of dystonia","volume":"40","year":"2025","journal-title":"Mov. 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