Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
7-29-2024
Journal
eLife
DOI
10.7554/eLife.91483
PMID
39072369
PMCID
PMC11286262
PubMedCentral® Posted Date
7-29-2024
PubMedCentral® Full Text Version
Post-print
Abstract
The 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.
Keywords
Animals, Tremor, Mice, Disease Models, Animal, Dystonia, Cerebellar Nuclei, Ataxia, Optogenetics, Action Potentials, Male, Female, Neurons, ataxia, cerebellum, classifier model, dystonia, mouse, neuroscience, optogenetics, tremor
Published Open-Access
yes
Recommended Citation
van der Heijden, Meike E; Brown, Amanda M; Kizek, Dominic J; et al., "Cerebellar Nuclei Cells Produce Distinct Pathogenic Spike Signatures in Mouse Models of Ataxia, Dystonia, and Tremor" (2024). Duncan NRI Faculty and Staff Publications. 100.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/100
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