TrackUSF, a novel tool for automated ultrasonic vocalization analysis, reveals modified calls in a rat model of autism.

BACKGROUND: Various mammalian species emit ultrasonic vocalizations (USVs), which reflect their emotional state and mediate social interactions. USVs are usually analyzed by manual or semi-automated methodologies that categorize discrete USVs according to their structure in the frequency-time domains. This laborious analysis hinders the effective use of USVs as a readout for high-throughput analysis of behavioral changes in animals. RESULTS: Here we present a novel automated open-source tool that utilizes a different approach towards USV analysis, termed TrackUSF. To validate TrackUSF, we analyzed calls from different animal species, namely mice, rats, and bats, recorded in various settings and compared the results with a manual analysis by a trained observer. We found that TrackUSF detected the majority of USVs, with less than 1% of false-positive detections. We then employed TrackUSF to analyze social vocalizations in Shank3-deficient rats, a rat model of autism, and revealed that these vocalizations exhibit a spectrum of deviations from appetitive calls towards aversive calls. CONCLUSIONS: TrackUSF is a simple and easy-to-use system that may be used for a high-throughput comparison of ultrasonic vocalizations between groups of animals of any kind in any setting, with no prior assumptions.

Simultaneous recording of ultrasonic vocalizations and sniffing from socially interacting individual rats using a miniature microphone.

Vocalizations are pivotal in mammalian communication, especially in humans. Rodents accordingly rely on ultrasonic vocalizations (USVs) that reflect their internal state as a primary channel during social interactions. However, attributing vocalizations to specific individuals remains challenging, impeding internal state assessment. Rats emit 50-kHz USVs to indicate positive states and intensify sniffing during alertness and social interactions. Here, we present a method involving a miniature microphone attached to the rat nasal cavity that allows to capture both male and female individual rat vocalizations and sniffing patterns during social interactions. We found that while the emission of 50-kHz USVs increases during close interactions, these signals lack specific behavioral associations. Moreover, a previously unreported low-frequency vocalization type marking rat social interactions was uncovered. Finally, different dynamics of sniffing and vocalization activities point to distinct underlying internal states. Thus, our method facilitates the exploration of internal states concurrent with social behaviors.

Distinct Dynamics of Theta and Gamma Rhythmicity during Social Interaction Suggest Differential Mode of Action in the Medial Amygdala of Sprague Dawley Rats and C57BL/6J Mice.

The medial nucleus of the amygdala (MeA) is known to regulate social behavior. This brain area is functionally positioned in a crossroads between sensory information processing and behavioral modulation. On the one hand, it receives direct chemosensory input from the accessory olfactory bulb. On the other hand, it orchestrates various behavioral outputs via brain-wide projections under the regulation of multiple neuromodulatory systems. Previously, we showed that adult male Sprague Dawley (SD) rats and C57BL/6J mice, the most widely used rodent models in neuroscience research, differ in their dynamics of motivation to interact with a novel same-sex conspecific and that this difference correlates with the level of c-Fos expression in the MeA. Here we used chronically implanted electrodes to compare rhythmic local field potential signals recorded from these animals during free and restricted social interactions. We found a significant induction of rhythmicity in the theta (4-12 Hz) and gamma (30-80 Hz) bands during both free and restricted social interaction in both rats and mice. However, the induction of gamma rhythmicity, thought to reflect activity of local neuronal networks, was significantly higher in rats than mice. Nevertheless, in contrast to rats, mice exhibited induction of rhythmicity, in both the theta and gamma bands, in synchrony with investigation of social, but not object stimuli. These results suggest that during interaction with a novel same-sex conspecific, the MeA of C57BL/6J mice is mostly involved in sensory information processing while in SD rats it is mainly active in modulating the social motivation state of the animal.