A comprehensive analysis of adult ultrasonic vocalizations in Cntnap2 knockout mice reveals quantitative, qualitative, and sex-specific differences.

Communicative deficits are a core feature of autism spectrum disorder (ASD) that present early in development and persist into adulthood. The majority of studies focus exclusively on early life communication, therefore the mechanisms underlying adult communicative behaviors are unclear. The Cntnap2 gene is implicated in the onset of ASD deficits and is specifically vital for vocal communicative behaviors, however, its effects on adult communication are not known. To address this problem, we assessed vocal communicative behaviors known as ultrasonic vocalizations (USVs) in Cntnap2 wildtype (WT) and knockout (KO) adult mice as well as scent marking behaviors - a form of non-vocal communication. When assessing courtship USVs via a male-female pairing session, we found that KO males produced significantly fewer USVs with a shorter duration, higher pitch, and lower tonality than WT males. They also emitted fewer two-component call types and more downward and composite calls. In the female urine-induced communicative paradigm, we found that KO males emitted calls of a higher frequency, trended towards a decreased call rate, and produced significantly more complex and short call types but less frequency step calls relative to controls. No other changes in USVs were found nor were there any differences in scent marking behaviors between groups. Lastly, using the female resident-intruder paradigm, we found numerous changes in call type utilization, but no differences in the call rate nor the spectral and temporal features of the calls. Altogether, these findings indicate that the Cntnap2 gene selectively alters adult vocal communicative behaviors.