Social Behavior and Ultrasonic Vocalizations in a Genetic Rat Model Haploinsufficient for the Cross-Disorder Risk Gene Cacna1c

Abstract

The top-ranked cross-disorder risk gene CACNA1C is strongly associated with multiple neuropsychiatric dysfunctions. In a recent series of studies, we applied a genomically informed approach and contributed extensively to the behavioral characterization of a genetic rat model haploinsufficient for the cross-disorder risk gene Cacna1c. Because deficits in processing social signals are associated with reduced social functioning as commonly seen in neuropsychiatric disorders, we focused on socio-affective communication through 22-kHz and 50-kHz ultrasonic vocalizations (USV). Specifically, we applied a reciprocal approach for studying socio-affective communication in sender and receiver by including rough-and-tumble play and playback of 22-kHz and 50-kHz USV. Here, we review the findings obtained in this recent series of studies and link them to the key features of 50-kHz USV emission during rough-and-tumble play and social approach behavior evoked by playback of 22-kHz and 50-kHz USV. We conclude that Cacna1c haploinsufficiency in rats leads to robust deficits in socio-affective communication through 22-kHz and 50-kHz USV and associated alterations in social behavior, such as rough-and-tumble play behavior.

Keywords: Cav1.2; alarm call; animal model; calcium; playback; rough-and-tumble play; social approach; social contact call; social play; ultrasonic vocalization.

Figure 1

Exemplary spectrograms of ultrasonic vocalizations (USV) emitted by rats. (A) Spectrogram of 50-kHz USV serving as social contact calls. Please note the presence of different 50-kHz USV subtypes, including FLAT, STEP, TRILL, and MIXED calls. (B) Spectrogram of 22-kHz USV serving as alarm calls. Please note the difference in time scaling.

Figure 2

Effects of Cacna1c haploinsufficiency on (A) the emission of 50-kHz ultrasonic vocalizations (USV) emitted during rough-and-tumble play in the sender (filled orange squares = male Cacna1c^+/+ littermate controls; open orange squares = male Cacna1c^+/− rats; filled black circles = female Cacna1c^+/+ littermate controls; open white circles = female Cacna1c^+/− rats; N = 10 play pairs each) and (B) on social approach behavior evoked by playback of 50-kHz USV in the receiver (filled orange bars = male Cacna1c^+/+ littermate controls; open orange bars = male Cacna1c^+/− rats; filled black bars = female Cacna1c^+/+ littermate controls; open black bars = female Cacna1c^+/− rats; N = 20 rats each). Please note that social approach behavior is shown as change scores from baseline. Data were previously reported in [15,16]. * p < 0.05 vs. male Cacna1c^+/+ littermate controls; ^# p < 0.05 vs. baseline.