Cerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and 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 predicts the phenotypic presentation of cerebellar pathophysiology. 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 predicted 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.

Linking abnormal neural activity patterns to motor deficits

“…Now, in eLife, Meike van der Heijden, Amanda Brown, Dominic Kizek and Roy Sillitoe report that abnormal patterns of activity from a single set of neurons can be used to predict motor symptoms associated with multiple neurological disorders ( van der Heijden et al, 2024 ). Taking advantage of the information bottleneck at the cerebellar nuclei, the team – who are based at Baylor College of Medicine and Texas Children’s Hospital – measured the firing patterns of these neurons in mouse models of movement disorders.…”