Alterations in the ultrasonic vocalization sequences in pups of an autism spectrum disorder mouse model: A longitudinal study over age and sex

Social communication deficit is a hallmark of autism spectrum disorders (ASDs). Mouse ultrasonic-vocalizations (USVs), with communicative significance, are extensively used to probe vocalization-based social communication impairment. Despite the predictable nature of mouse USVs, very few studies have taken advantage of the same. The current work explores USV pup-isolation-call (PIC) features and alterations in structural content of predictive PIC sequences of the well-established in-utero valproic-acid (VPA) exposure-based ASDs model. Our study shows that along with call features, even higher-order USV structures undergo alterations in the ASDs model at all developmental ages and sexes. Confirming prior observations, we found reduced call rates and durations, as well as heightened peak frequencies in ASD model pups. Our data also highlights trends in call features, syllable composition, and transitions across sexes and age. The ASD female mice exhibited higher within group heterogeneity in syllable composition and transition over age compared to ASD males or typically developing males and females. Analysis of sequences of USVs emitted by pups using mutual information between syllables at different positions revealed that dependencies between syllables were higher in typically developing mice of both sexes compared to ASD model pups. In brief, we found that PICs call features were altered in VPA mouse models both for male and female pups and their vocalizations lack the complex syllable sequence order emitted by typically developing ones. Our studies will help establish and further investigate ASD mouse models to get a clearer picture of abnormalities related to social communication deficits over sexes and age.