Temporal dynamics of isolation calls emitted by pups in environmental and genetic mouse models of autism spectrum disorder.

Introduction: Environmental and genetic factors contribute to the increased risk for neurodevelopmental disorders, including deficits in the development of social communication. In the mouse, ultrasonic vocalizations emitted by the pup stimulate maternal retrieval and potentiate maternal care. Therefore, isolation induced ultrasonic vocalization emitted by pups provides a means to evaluate deficits in communication during early development, before other ways of communication are apparent. Previous studies in our labs showed that gestational exposure to the pesticide chlorpyrifos (CPF) and the Methylenetetrahydrofolate (Mthfr)-knock-out mice are associated with impaired social preference, restricted or repetitive behavior and altered spectral properties of pups' ultrasonic vocalization. In this study, we explore the temporal dynamics of pups' vocalization in these Autism spectrum disorder (ASD) models. Methods: We utilized the maternal potentiation protocol and analyzed the time course of pup vocalizations following isolation from the nest. Two models of ASD were studied: gestational exposure to the pesticide CPF and the Mthfr-knock-out mice. Results: Vocalization emitted by pups of both ASD models were dynamically modified in quantity and spectral structure within each session and between the two isolation sessions. The first isolation session was characterized by a buildup of call quantity and significant effects of USV spectral structure variables, and the second isolation session was characterized by enhanced calls and vocalization time, but minute effect on USV properties. Moreover, in both models we described an increased usage of harmonic calls with time during the isolation sessions. Discussion: Communication between two or more individuals requires an interplay between the two sides and depends on the response and the time since the stimulus. As such, the presence of dynamic changes in vocalization structure in the control pups, and the alteration observed in the pups of the ASD models, suggest impaired regulation of vocalization associated with the environmental and genetic factors. Last, we propose that temporal dynamics of ultrasonic vocalization communication should be considered in future analysis in rodent models of ASD to maximize the sensitivity of the study of vocalizations.