Mouse Ultrasonic Vocalization Analyses to Model Communication Deficits in Autism

Background: Delayed language and poor communication skills are fundamental to the diagnosis of autism. Mice utter distinct types of ultrasonic vocalizations, which differ depending on the animal’s age, its current affective state, and environmental factors. Infant mice emit ultrasonic vocalizations when isolated from their dam and litter. It is known that such ultrasonic vocalizations serve communicative purposes, since they elicit the mother’s exploratory behavior, facilitating her retrieval of isolated pups. Furthermore, it was shown that isolation-induced ultrasonic calling in mouse pups is dependent on the social context (Branchi et al., 1998; Oswalt & Meier, 1975). We are investigating the nature of the vocalizations emitted by pup, juvenile, and adult mice in various social situations, for subsequent applications to mouse models of autism.

Objectives: The objective of the present study was to test whether the social context affects isolation-induced ultrasonic vocalizations in mouse pups and adults.  Optimized methods are being tested with the inbred strain BTBR T+tf/J (BTBR), a mouse model of autism with well-replicated social deficits, unusual calls, and repetitive behaviors, as well as in knockout mice with mutations in candidate genes for autism.

Methods: Isolated mouse pups were compared for quieting responses. To induce ultrasonic calling, 2-12 day old pups were removed from the home cage for 5 min at room temperature. Half of the litter was tested in clean bedding and the other half in soiled bedding from the home cage, which contained maternal odor. In a second paradigm, vocalizations were recorded in adult male mice in an open field containing an aliquot of adult female urine.  Ultrasonic vocalizations were monitored with a CM16 ultrasound microphone, recorded by Avisoft-RECORDER and analyzed with Avisoft-SASLabPro (Avisoft Bioacoustics, Germany).  Experiments were conducted in each social situation to compare C57BL/6J (B6), a highly social inbred strain of mice, with BTBR, and to compare mutant lines of mice with their wildtype littermates.

Results: When isolated from dam and litter, both B6 and BTBR pups vocalized. BTBR pups vocalized more than B6 pups, as previously reported (Scattoni et al., 2008). Preliminary data indicate that B6 displayed quieting in the presence of their home cage litter containing maternal odors, while BTBR did not. When placed in an open field containing female urine, ultrasonic vocalizations were emitted by some, but not all, male mice. Preliminary data indicate that some individuals consistently call and some individuals consistently do not call, when tested in repeated sessions. 

Conclusions: Ultrasonic vocalizations appear to differ between individual mice and between strains of mice.  Early results employing these two social situation tasks suggest that analyses of mouse vocalizations may offer assays relevant to communication deficits in autism.