Sex and age independent predictive call sequence alterations of pups in an autism spectrum disorder mouse model

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. However, most studies on ASDs mouse-models show inconsistent alterations in USVs based phenotypes over age and sex. 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 the importance of higher-order USV structures, with speech-like sequential dependencies that have consistent alterations in ASDs model at all developmental ages and sex. In addition to confirming prior observations of reduced call rates and durations, as well as heightened peak frequencies in ASD model pups, our data underscores inconsistent trends in the call features across sex and age. The varying nature of call features in ASD models poses a substantial challenge in assessing intervention outcomes. The above inconsistency complicates the differentiation between the effects of aging and therapeutic impacts. Establishing consistent alteration in USVs could help uncover age- and sex-independent changes in ASD models, shedding light on associated therapeutics and developmental mechanisms. ### Competing Interest Statement The authors have declared no competing interest.