Assessing vocal changes through spectral analyses of vocalizations in a cerebellar-specific dystonia mouse model.

Abstract

Vocal impairments are a debilitating but understudied feature of several dystonias, including generalized and early-onset genetic forms. Despite growing recognition that cerebellar dysfunction contributes to dystonic pathophysiology, the circuit mechanisms underlying vocal-motor abnormalities remain poorly understood, and effective treatments remain limited, in part due to the lack of a preclinical model that captures specific vocal features. Our experiment evaluates ultrasonic vocalizations (USVs) in Ptf1a ^Cre/+ ;Vglut2 ^fl/fl mice, a cerebellum-specific generalized dystonia model, to assess cerebellar contributions to phonation and explore translational relevance for vocal features. At postnatal day 9, dystonic mice demonstrated statistically significant reductions in total USV count, relative count of complex calls, and key spectral parameters-especially frequency modulation and power-mirroring general phonatory abnormalities seen in dystonia. Cluster analyses further revealed impaired vocal burst initiation, suggesting disrupted cerebellar coordination of temporal vocal-motor output. These findings support the model's construct and face validity for studying cerebellar mechanisms of vocal impairment. By identifying quantifiable acoustic disruptions, our study establishes a foundational platform for future circuit-targeted investigations of vocal-motor dysfunction in dystonia.