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Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (\n                    <jats:italic>\n                      Gnal\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice carry a heterozygous knockout mutation of the\n                    <jats:italic>Gnal<\/jats:italic>\n                    gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode,\n                    <jats:italic>\n                      Gnal\n                      <jats:sup>+\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after \u03b8-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.\n                  <\/jats:p>","DOI":"10.7554\/elife.79135","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T07:15:22Z","timestamp":1653894922000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.79135","source":"Crossref","is-referenced-by-count":29,"title":["Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia"],"prefix":"10.7554","volume":"11","author":[{"given":"Hind Baba","family":"A\u00efssa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013cjyk83","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurophysiology of Brain Circuits Team, Institut de biologie de l'Ecole normale sup\u00e9rieure 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