Ultrasonic vocalizations during male-female interaction in the mouse model of Down syndrome Ts65Dn

Down syndrome (DS) is the leading cause of genetically defined intellectual disability. Although speech and language impairments are salient features of this disorder, the nature of these phenotypes and the degree to which they are exacerbated by concomitant oromotor dysfunction and/or hearing deficit are poorly understood. Mouse models like Ts65Dn, the most extensively used DS animal model, have been critical to understanding the genetic and developmental mechanisms that contribute to intellectual disability. In the present study, we characterized the properties of the ultrasonic vocalizations (USVs) emitted by Ts65Dn males during courtship episodes with female partners. USVs emitted by mice in this setting have been proposed to have some basic correlation to human speech. Data were collected and analyzed from 22 Ts65Dn mice and 22 of their euploid littermates. We found that both the minimum and maximum peak frequencies of Ts65Dn calls were lower than those produced by euploid mice, whereas the mean individual duration of "down" and "complex" syllable types was significantly longer. Peak, minimal and maximal, and the fundamental frequencies of short syllables generated by Ts65Dn mice were lower compared to those by euploid mice. Finally, Ts65Dn males made fewer multiple jumps calls during courtship and the mean total duration of their "arc", "u", and "complex" syllables was longer. We discuss the human correlates to these findings, their translational potential, and the limitations of this approach. To our knowledge, this is the first characterization of differences between adult Ts65Dn and euploid control mice with respect to USVs.