{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:51:53Z","timestamp":1781920313138,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001595","name":"Dystonia Medical Research Foundation","doi-asserted-by":"publisher","award":["DMRF\u2010BCAD\u20102024\u20104"],"award-info":[{"award-number":["DMRF\u2010BCAD\u20102024\u20104"]}],"id":[{"id":"10.13039\/100001595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"\n Abstract<\/jats:title>\n \n Cerebellar dysfunction can cause ataxia, dystonia, and tremor. Cerebellar nuclei neurons, the main cerebellar output neurons, exhibit distinct spike patterns in mouse models for different movement disorders. However nuclei spike pattern changes often arise from misfiring, miswiring, or degenerating Purkinje cells, which form the predominant input onto nuclei cells. It is often assumed that changes in Purkinje cell spike patterns cause inverse changes in nuclei cell spike patterns because Purkinje cells form GABAergic synapses onto cerebellar nuclei cells. We test this hypothesis by investigating whether a systematic relationship between spike patterns in Purkinje and nuclei cells exists. We analysed parameters relating to spike rate and irregularity from single\u2010cell\n in vivo<\/jats:italic>\n electrophysiological recordings of cerebellar cells in five mouse models for cerebellar movement disorders. We examined whether changes in steady\u2010state Purkinje cell spike patterns could predict nuclei cell spike pattern changes. We found that some parameters for steady\u2010state spike irregularity were positively correlated between Purkinje and nuclei cells, but no \u2013 especially no inverse \u2013 relationship was observed between steady\u2010state Purkinje and nuclei cell spike rate. We also did not observe an increased steady\u2010state nuclei cell spike rate in mice with silenced or degenerating Purkinje cells. Because we find no systematic relationship between steady\u2010state Purkinje and nuclei spike activity, it is not possible to reliably predict disease\u2010associated nuclei spike patterns based on single\u2010cell Purkinje recordings. Moreover, normal Purkinje cell spike patterns can mask disease\u2010causing spike patterns in cerebellar nuclei cells, underscoring the importance of studying cerebellar nuclei cell function in cerebellar disease.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n This study tests the hypothesis that cerebellar Purkinje cell spike rates inversely change with nuclei cell spike rates in cerebellar disease models.<\/jats:p>\n <\/jats:list-item>\n \n We found no reliable correlation in steady\u2010state spike rate parameters between Purkinje and nuclei cells; across mouse models differences in Purkinje cell firing rate were not reliably associated with differences in nuclei cell firing rate.<\/jats:p>\n <\/jats:list-item>\n \n We observed a positive correlation for steady\u2010state spike irregularity between Purkinje and nuclei cells, but also found nuclei cell irregularity changes in mice without Purkinje cell spike irregularity.<\/jats:p>\n <\/jats:list-item>\n \n The findings emphasize the need to directly study nuclei cell function in cerebellar disease, as Purkinje cell spike patterns do not reliably correlate with nuclei cell changes or even mask disease states.<\/jats:p>\n <\/jats:list-item>\n \n The complex relationship may stem from nuclei cell's intrinsic adaptive properties, developmental compensation, or converging Purkinje cell inputs.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290000","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T03:45:35Z","timestamp":1776743135000},"page":"3964-3983","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Steady\u2010state Purkinje cell activity has limited predictive power for cerebellar output in disease"],"prefix":"10.1113","volume":"604","author":[{"given":"Alyssa M","family":"Lyon","sequence":"first","affiliation":[{"name":"Fralin Biomedical Research Institute Virginia Tech Carilion Roanoke Virginia USA"},{"name":"Graduate Program in Translation Biology, Medicine, and Health Virginia Tech Roanoke Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Hernandez\u2010Castanon","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute Virginia Tech Carilion Roanoke Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike E","family":"van der Heijden","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute Virginia Tech Carilion Roanoke Virginia USA"},{"name":"Center for Neurobiology Research Virginia Tech Carilion Roanoke Virginia USA"},{"name":"School of Neuroscience Virginia Tech Blacksburg Virginia USA"},{"name":"Department of Pediatrics Virginia Tech Carilion Roanoke Virginia 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