Courtship and distress ultrasonic vocalizations are disrupted in a mouse model of Angelman syndrome.

BACKGROUND

Angelman syndrome (AS) is a single-gene neurodevelopmental disorder caused by loss of function of the maternal copy of the gene. Nearly all individuals with AS lack speech, resulting in major impacts on daily life for patients and caregivers. To evaluate new therapies for AS, it is crucial to have a mouse model that characterizes meaningful clinical features. Vocalizations are used in many contexts in mice, including pup retrieval, social interactions, courtship, and distress. Previous work in the mouse model of AS found abnormalities in the number of ultrasonic vocalizations (USVs) mice produced during pup isolation and same-sex social interactions. Here, we evaluated vocalizations during courtship and distress. Quantifying USVs in these contexts enables comparison of USVs in social (courtship) and non-social (distress) settings. In addition, we assessed the utility of incorporating USV testing into existing mouse behavioral assessments used to evaluate potential AS treatments.

METHODS

We used a three-chamber social preference test for courtship vocalizations and a tail suspension test for distress vocalizations in adult wild-type (WT) and littermates, and quantified USV properties using the program DeepSqueak. Next, mice performed an established behavioral battery that included rotarod, open field, marble burying, and nest building. We used principal component analysis to evaluate the value of USV testing in the context of other behaviors.

RESULTS

In both social courtship and nonsocial distress behavioral paradigms, mice made fewer USVs compared to WT mice. Spectral properties of USVs were abnormal in mice on the courtship test but mostly typical on the distress test. Including USVs in the mouse behavior battery increased the distance between and WT clusters in principal component space.

CONCLUSIONS

mice have difficulty producing USVs in social and nonsocial contexts. Spectral properties of USVs are most impacted in the social courtship context. Adding USVs to the behavior battery may improve sensitivity to detect group differences and changes in communication.