Cerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and tremor

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dc.contributor.authorvan der Heijden, Meike E.en
dc.contributor.authorBrown, Amanda M.en
dc.contributor.authorKizek, Dominic J.en
dc.contributor.authorSillitoe, Royen
dc.date.accessioned2024-12-02T15:30:51Zen
dc.date.available2024-12-02T15:30:51Zen
dc.date.issued2024-07-29en
dc.description.abstractThe cerebellum contributes to a diverse array of motor conditions, including ataxia, dystonia, and tremor. The neural substrates that encode this diversity are unclear. Here, we tested whether the neural spike activity of cerebellar output neurons is distinct between movement disorders with different impairments, generalizable across movement disorders with similar impairments, and capable of causing distinct movement impairments. Using in vivo awake recordings as input data, we trained a supervised classifier model to differentiate the spike parameters between mouse models for ataxia, dystonia, and tremor. The classifier model correctly assigned mouse phenotypes based on single-neuron signatures. Spike signatures were shared across etiologically distinct but phenotypically similar disease models. Mimicking these pathophysiological spike signatures with optogenetics induced the predicted motor impairments in otherwise healthy mice. These data show that distinct spike signatures promote the behavioral presentation of cerebellar diseases.en
dc.description.versionPublished versionen
dc.format.extent28 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN RP91483 (Article number)en
dc.identifier.doihttps://doi.org/10.7554/eLife.91483en
dc.identifier.eissn2050-084Xen
dc.identifier.issn2050-084Xen
dc.identifier.orcidvan der Heijden, Meike [0000-0003-0801-8806]en
dc.identifier.other91483 (PII)en
dc.identifier.pmid39072369en
dc.identifier.urihttps://hdl.handle.net/10919/123673en
dc.identifier.volume12en
dc.language.isoenen
dc.publishereLifeen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/39072369en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcerebellumen
dc.subjectataxiaen
dc.subjectdystoniaen
dc.subjecttremoren
dc.subjectclassifier modelen
dc.subjectoptogeneticsen
dc.subjectMouseen
dc.subject.meshCerebellar Nucleien
dc.subject.meshNeuronsen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshAtaxiaen
dc.subject.meshDystoniaen
dc.subject.meshTremoren
dc.subject.meshDisease Models, Animalen
dc.subject.meshAction Potentialsen
dc.subject.meshFemaleen
dc.subject.meshMaleen
dc.subject.meshOptogeneticsen
dc.titleCerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and tremoren
dc.title.serialeLifeen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-groupVirginia Techen
pubs.organisational-groupVirginia Tech/Scienceen
pubs.organisational-groupVirginia Tech/Faculty of Health Sciencesen
pubs.organisational-groupVirginia Tech/All T&R Facultyen
pubs.organisational-groupVirginia Tech/Science/COS T&R Facultyen
pubs.organisational-groupVirginia Tech/Science/School of Neuroscienceen

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