The E3 ubiquitin ligase Ube3a is an important regulator of activity-dependent synapse development and plasticity. Ube3a mutations cause Angelman syndrome and have been associated with autism spectrum disorders (ASD). However, the biological significance of alternative Ube3a transcripts generated in mammalian neurons remains unknown. We report here that Ube3a1 RNA, a transcript that encodes a truncated Ube3a protein lacking catalytic activity, prevents exuberant dendrite growth and promotes spine maturation in rat hippocampal neurons. Surprisingly, Ube3a1 RNA function was independent of its coding sequence but instead required a unique 3' untranslated region and an intact microRNA pathway. Ube3a1 RNA knockdown increased activity of the plasticity-regulating miR-134, suggesting that Ube3a1 RNA acts as a dendritic competing endogenous RNA. Accordingly, the dendrite-growth-promoting effect of Ube3a1 RNA knockdown in vivo is abolished in mice lacking miR-134. Taken together, our results define a noncoding function of an alternative Ube3a transcript in dendritic protein synthesis, with potential implications for Angelman syndrome and ASD.

No abstract

Rats emit distinct types of ultrasonic vocalizations (USV), which serve as situation-dependent affective signals with important communicative functions. Low-frequency 22-kHz USV typically occur in aversive situations, such as social defeat, whereas high-frequency 50-kHz USV can be observed in appetitive situations, like rough-and-tumble-play in juveniles or mating in adults. The 2 main USV types serve distinct communicative functions and induce call-specific behavioral responses in the receiver. While 22-kHz USV probably serve as alarm calls, 50-kHz USV appear to serve a prosocial communicative function in the sexual and the nonsexual context. In the sexual context, however, this view has recently been challenged by playback studies where only very limited behavioral changes were observed in response to prosocial 50-kHz USV. The aim of the present study was therefore to test whether female rats display social approach behavior in response to male prosocial 50-kHz USV by means of our established playback paradigm. To this aim, we exposed female rats to playback of the following 2 acoustic stimuli: (a) natural male 50-kHz USV and (b) time- and amplitude-matched white noise, with the latter serving as acoustic control for novelty-induced changes in behavior not linked to the communicative function of male prosocial 50-kHz USV. Our present findings show that female rats display high levels of social approach behavior in response to male prosocial 50-kHz USV, but not time- and amplitude-matched white noise, supporting the conclusion that male prosocial 50-kHz USV are likely to play an important role in establishing social proximity and possibly regulate mating behavior.

Rats are highly social animals and social play during adolescence has an important role for social development, hence post-weaning social isolation is widely used to study the adverse effects of juvenile social deprivation and to induce behavioral phenotypes relevant to neuropsychiatric disorders, like schizophrenia. Communication is an important component of the rat's social behavior repertoire, with ultrasonic vocalizations (USV) serving as situation-dependent affective signals. High-frequency 50-kHz USV occur in appetitive situations and induce approach behavior, supporting the notion that they serve as social contact calls; however, post-weaning isolation effects on the behavioral changes displayed by the receiver in response to USV have yet to be studied. We therefore investigated the impact of post-weaning isolation on socio-affective information processing as assessed by means of our established 50-kHz USV radial maze playback paradigm. We showed that post-weaning social isolation specifically affected the behavioral response to playback of pro-social 50-kHz but not alarm 22-kHz USV. While group-housed rats showed the expected preference, i.e., approach, toward 50-kHz USV, the response was even stronger in short-term isolated rats (i.e., 1 day), possibly due to a higher level of social motivation. In contrast, no approach was observed in long-term isolated rats (i.e., 4 weeks). Importantly, deficits in approach were reversed by peer-mediated re-socialization and could not be observed after post-adolescent social isolation, indicating a critical period for social development during adolescence. Together, these results highlight the importance of social experience for affiliative behavior, suggesting a critical involvement of play behavior on socio-affective information processing in rats.

Rats are able to produce ultrasonic vocalizations (USVs). Such USVs are an important component of the rat social behavior repertoire and serve distinct communicative functions as socio-affective signals. Depending on the emotional valence of the situation, juvenile and adult rats utter (1) aversive 22-kHz USVs conveying an appeasing and/or alarming function; or (2) appetitive 50-kHz USVs, which act as social contact calls, amongst others. A 50-kHz USV radial maze playback paradigm that allows assessment of the behavioral responses displayed by the recipients in a highly standardized manner has been developed. In this newly developed paradigm, a rat is exposed individually to playback of natural 50-kHz USVs and appropriate acoustic control stimuli using an acoustic presentation system for ultrasound. By this means, it has been consistently shown that 50-kHz USVs lead to social approach behavior in the recipient, supporting the notion that they serve an affiliative function as social contact calls.