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However, the neural abnormalities that promote the resultant motor dysfunctions remain elusive. Studies in humans show that some non\u2010manifesting DYT6 carriers have altered cerebello\u2010thalamo\u2010cortical function with subtle but reproducible tremor. Here, we uncover that <jats:italic>Thap1<\/jats:italic> heterozygote mice have action tremor that rises above normal baseline values even though they do not exhibit overt dystonia\u2010like twisting behaviour. At the neural circuit level, we show using <jats:italic>in vivo<\/jats:italic> recordings in awake <jats:italic>Thap1<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice that Purkinje cells have abnormal firing patterns and that cerebellar nuclei neurons, which connect the cerebellum to the thalamus, fire at a lower frequency. Although the <jats:italic>Thap1<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice have fewer Purkinje cells and cerebellar nuclei neurons, the number of long\u2010range excitatory outflow projection neurons is unaltered. The preservation of interregional connectivity suggests that abnormal neural function rather than neuron loss instigates the network dysfunction and the tremor in <jats:italic>Thap1<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice. Accordingly, we report an inverse correlation between the average firing rate of cerebellar nuclei neurons and tremor power. Our data show that cerebellar circuitry is vulnerable to <jats:italic>Thap1<\/jats:italic> mutations and that cerebellar dysfunction may be a primary cause of tremor in non\u2010manifesting DYT6 carriers and a trigger for the abnormal postures in manifesting patients.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp280978","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T20:55:17Z","timestamp":1609188917000},"page":"2037-2054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Abnormal cerebellar function and tremor in a mouse model for non\u2010manifesting partially penetrant dystonia type 6"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0801-8806","authenticated-orcid":false,"given":"Meike E.","family":"van der Heijden","sequence":"first","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine  Houston TX 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