<i>Cacna1c</i> haploinsufficiency leads to pro-social 50-kHz ultrasonic communication deficits in rats

Abstract

The cross-disorder risk gene <i>CACNA1C</i> is strongly implicated in multiple neuropsychiatric disorders, including autism spectrum disorder (ASD), bipolar disorder (BPD) and schizophrenia (SCZ), with deficits in social functioning being common for all major neuropsychiatric disorders. In the present study, we explored the role of <i>Cacna1c</i> in regulating disorder-relevant behavioral phenotypes, focusing on socio-affective communication after weaning during the critical developmental period of adolescence in rats. To this aim, we used a newly developed genetic <i>Cacna1c</i> rat model and applied a truly reciprocal approach for studying communication through ultrasonic vocalizations, including both sender and receiver. Our results show that a deletion of <i>Cacna1c</i> leads to deficits in social behavior and pro-social 50-kHz ultrasonic communication in rats. Reduced levels of 50-kHz ultrasonic vocalizations emitted during rough-and-tumble play may suggest that <i>Cacna1c</i> haploinsufficient rats derive less reward from playful social interactions. Besides the emission of fewer 50-kHz ultrasonic vocalizations in the sender, <i>Cacna1c</i> deletion reduced social approach behavior elicited by playback of 50-kHz ultrasonic vocalizations. This indicates that <i>Cacna1c</i> haploinsufficiency has detrimental effects on 50-kHz ultrasonic communication in both sender and receiver. Together, these data suggest that <i>Cacna1c</i> plays a prominent role in regulating socio-affective communication in rats with relevance for ASD, BPD and SCZ.This article has an associated First Person interview with the first author of the paper.