Cerebellar Nuclei Cells Produce Distinct Pathogenic Spike Signatures in Mouse Models of Ataxia, Dystonia, and Tremor

Authors

Meike E van der Heijden
Amanda M Brown
Dominic J Kizek
Roy V Sillitoe

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

Published Open-Access

yes

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

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.