Distinct developmental trajectories of pup ultrasonic vocalizations across ASD mouse models without increased variability

20/09/2026

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Comparative analysis across VPA treated, Caps2-/- and Chd8+/- pups found call rate changes peak at postnatal day 9, with differing direction and magnitude.
VPA treated and Caps2-/- pups showed shorter call duration and simplified frequency structure; Chd8+/- showed minimal acoustic alterations.
Within-group variability in call rate and acoustic features was comparable across all models and controls, indicating model specific developmental shifts.

Behav Brain Res. 2026 Sep 19:116486. doi: 10.1016/j.bbr.2026.116486. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) is characterized by impairments in social communication. Pup ultrasonic vocalizations (USVs), a widely used measure of early social communication in mouse models, have yielded inconsistent findings across studies, hindering cross-model comparisons. Here, we systematically compared isolation-induced pup USVs across three ASD mouse models with distinct etiologies: valproic acid (VPA)-treated, Caps2^-/-, and Chd8^+/- mice. Alterations in call rate were most pronounced at postnatal day 9, corresponding to the developmental peak of USV production, but both the direction and magnitude of these changes differed across models. VPA-treated and Caps2^-/- mice exhibited shortened call duration and simplified frequency structure, whereas Chd8^+/- mice showed minimal acoustic alterations. Notably, despite clear differences in mean USV features, within-group variability in call rate and acoustic properties was comparable across all models, including controls. These findings indicate that ASD-related alterations in pup USVs reflect model-specific shifts in developmental trajectories rather than increased inter-individual variability.

PMID:42763055 | DOI:10.1016/j.bbr.2026.116486

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