Oxytocin receptors influence the development and maintenance of social behavior in zebrafish (Danio rerio).

Zebrafish are highly social teleost fish and an excellent model to study social behavior. The neuropeptide Oxytocin is associated different social behaviors as well as disorders resulting in social impairment like autism spectrum disorder. However, how Oxytocin receptor signaling affects the development and expression kinetics of social behavior is not known. In this study we investigated the role of the two oxytocin receptors, Oxtr and Oxtrl, in the development and maintenance of social preference and shoaling behavior in 2- to 8-week-old zebrafish. Using CRISPR/Cas9 mediated oxtr and oxtrl knock-out fish, we found that the development of social preference is accelerated if one of the Oxytocin receptors is knocked-out and that the knock-out fish reach significantly higher levels of social preference. Moreover, oxtr-/- fish showed impairments in the maintenance of social preference. Social isolation prior to testing led to impaired maintenance of social preference in both wild-type and oxtr and oxtrl knock-out fish. Knocking-out either of the Oxytocin receptors also led to increased group spacing and reduced polarization in a 20-fish shoal at 8 weeks post fertilization, but not at 4. These results show that the development and maintenance of social behavior is influenced by the Oxytocin receptors and that the effects are not just pro- or antisocial, but dependent on both the age and social context of the fish.

The neuropeptide Pth2 dynamically senses others via mechanosensation.

Species that depend on membership in social groups for survival exhibit changes in neuronal gene expression and behaviour when they face restricted social interactions or isolation1-3. Here we show that, across the lifespan of zebrafish (Danio rerio), social isolation specifically decreased the level of transcription of pth2, the gene that encodes the vertebrate-specific neuropeptide Pth2. However, 30 minutes of exposure to conspecifics was sufficient to initiate a significant rescue of pth2 transcript levels in previously isolated zebrafish. Transcription of pth2 exhibited bidirectional dynamics; following the acute isolation of socially reared fish, a rapid reduction in the levels of pth2 was observed. The expression of pth2 tracked not only the presence of other fish but also the density of the group. The sensory modality that controls the expression of pth2 was neither visual nor chemosensory in origin but instead was mechanical, induced by the movements of neighbouring fish. Chemical ablation of the mechanosensitive neuromast cells within the lateral line of fish prevented the rescue of pth2 levels that was induced by the social environment. In addition, mechanical perturbation of the water at frequencies similar to the movements of the zebrafish tail was sufficient to rescue the levels of pth2 in previously isolated fish. These data indicate a previously underappreciated role for the relatively unexplored neuropeptide Pth2 in both tracking and responding to the population density of the social environment of an animal.