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DMD is caused by mutations in the dystrophin gene, which result in extremely low or total loss of dystrophin protein expression. In the brain, dystrophin is heavily localized to cerebellar Purkinje cells, which control motor and non-motor functions. In vitro experiments in mouse Purkinje cells revealed that loss of dystrophin leads to low firing rates and high spiking variability. However, it is still unclear how the loss of dystrophin affects cerebellar function in the intact brain. Here, we used in vivo electrophysiology to record Purkinje cells and cerebellar nuclear neurons in awake and anesthetized female mdx (also known as Dmd) mice. Purkinje cell simple spike firing rate is significantly lower in mdx mice compared to controls. Although simple spike firing regularity is not affected, complex spike regularity is increased in mdx mutants. Mean firing rate in cerebellar nuclear neurons is not altered in mdx mice, but their local firing pattern is irregular. Based on the relatively well-preserved cytoarchitecture in the mdx cerebellum, our data suggest that faulty signals across the circuit between Purkinje cells and cerebellar nuclei drive the abnormal firing activity. The in vivo requirements of dystrophin during cerebellar circuit communication could help explain the motor and cognitive anomalies seen in individuals with DMD.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.040840","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T15:19:17Z","timestamp":1573226357000},"source":"Crossref","is-referenced-by-count":18,"title":["<i>In vivo<\/i> cerebellar circuit function is disrupted in an <i>mdx<\/i> mouse model of Duchenne muscular dystrophy"],"prefix":"10.1242","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9849-8924","authenticated-orcid":false,"given":"Trace L.","family":"Stay","sequence":"first","affiliation":[{"name":"Baylor College of Medicine 1 Department of Pathology and Immunology , , Houston, TX 77030 , USA"},{"name":"Baylor College of Medicine 2 Department of Neuroscience , , Houston, TX 77030 , USA"},{"name":"Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital 3 , 1250 Moursund Street, Suite 1325, Houston, TX 77030 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9229-1834","authenticated-orcid":false,"given":"Lauren N.","family":"Miterko","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine 1 Department of Pathology and Immunology , , Houston, TX 77030 , USA"},{"name":"Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital 3 , 1250 Moursund Street, Suite 1325, Houston, TX 77030 , USA"},{"name":"Baylor College of Medicine 4 Program in Developmental Biology , , Houston, TX 77030 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-6180","authenticated-orcid":false,"given":"Marife","family":"Arancillo","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital 3 , 1250 Moursund Street, Suite 1325, Houston, TX 77030 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Lin","sequence":"additional","affiliation":[{"name":"Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital 3 , 1250 Moursund Street, Suite 1325, Houston, TX 77030 , 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":"Baylor College of Medicine 1 Department of Pathology and Immunology , , Houston, TX 77030 , USA"},{"name":"Baylor College of Medicine 2 Department of Neuroscience , , Houston, TX 77030 , USA"},{"name":"Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital 3 , 1250 Moursund Street, Suite 1325, Houston, TX 77030 , USA"},{"name":"Baylor College of Medicine 4 Program in Developmental Biology , , Houston, TX 77030 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"2024061302394318900_DMM040840C1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1126\/science.aau1549","article-title":"Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy","volume":"362","author":"Amoasii","year":"2018","journal-title":"Science"},{"key":"2024061302394318900_DMM040840C2","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/brain\/awf012","article-title":"Brain function in Duchenne muscular dystrophy","volume":"125","author":"Anderson","year":"2002","journal-title":"Brain"},{"key":"2024061302394318900_DMM040840C3","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/mus.21467","article-title":"Enhanced homosynaptic LTD in cerebellar Purkinje cells of the dystrophic mdx mouse","volume":"41","author":"Anderson","year":"2010","journal-title":"Muscle Nerve"},{"key":"2024061302394318900_DMM040840C4","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1007\/s12311-018-0952-3","article-title":"Cerebellar modules and their role as operational cerebellar processing units: a consensus paper","volume":"17","author":"Apps","year":"2018","journal-title":"Cerebellum"},{"key":"2024061302394318900_DMM040840C5","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1152\/jn.00586.2014","article-title":"In vivo analysis of Purkinje cell firing properties during postnatal mouse development","volume":"113","author":"Arancillo","year":"2015","journal-title":"J. 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