Oxytocin receptor signalling modulates novelty recognition but not social preference in zebrafish

Abstract

| INTRODUC TI ONNonapeptides are known to be important players in the regulation of social behaviour across taxa. 1 They evolved from a common ancestral molecule, the arginine vasotocin, after a gene duplication event in early-jawed fish. 2 One copy originated the vasopressin-like peptides, which retained the most primitive functions of the ancestral molecule, namely the regulation of osmotic balance. The other originated the oxytocin (OXT)-like peptides, which have greatly diverged across species, being recruited for diverse homeostatic processes, including parturition and lactation in mammals. Throughout evolution, these nonapeptides have also been involved in the regulation of social behaviours, with vasopressin being more involved in aggression and agonistic behaviours and OXT in affiliative behaviours and sociality. 3 AbstractSociality is a complex phenomenon that involves the individual´s motivation to approach their conspecifics, along with social cognitive functions that enable individuals to interact and survive. The nonapeptide oxytocin (OXT) is known to regulate sociality in many species. However, the role of OXT in specific aspects of sociality is still not well understood. In the present study, we investigated the contribution of the OXT receptor (OXTR) signalling in two different aspects of zebrafish social behaviour: social preference, by measuring their motivation to approach a shoal of conspecifics, and social recognition, by measuring their ability to discriminate between a novel and familiar fish, using a mutant zebrafish lacking a functional OXTR. Although oxtr mutant zebrafish displayed normal attraction to a shoal of conspecifics, they exhibited reduced social recognition. We further investigated whether this effect would be social-domain specific by replacing conspecific fish by objects. Although no differences were observed in object approach, oxtr mutant fish also exhibited impaired object recognition. Our findings suggest that OXTR signalling regulates a more general memory recognition of familiar vs novel entities, not only in social but also in a non-social domain, in zebrafish. K E Y W O R D Sautism spectrum disorders, oxytocin, social preference, social recognition, zebrafish S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section.

Nurturing nature

“…Regardless of whether they were raised with mutants or non-mutants, fish that lacked the gene for the oxytocin receptor were always worse at discriminating between a familiar and an unfamiliar fish -a result predicted by previous studies (Ribeiro et al, 2020b). However, other experiments revealed that only mutant fish raised with other mutants were more reluctant to approach other fish and to integrate into a shoal.…”

Genetic variation in the social environment affects behavioral phenotypes of oxytocin receptor mutants in zebrafish

“…In contrast, when we tested social recognition, which is a form of social memory needed for individuality in social interactions (i.e. differential expression of social behavior depending on identity of interacting individual), that is known to be modulated by oxytocin both in mammals and zebrafish (21,22), we observed that oxtr (-/-) individuals exhibit a deficit in acquisition and retention of social recognition irrespective of the social environment ( oxtr (-/-) or oxtr (+/+) ) in which they were raised (F 1,44 = 7.600, p = 0.008; Figure 1F).…”

“…The social preference test assesses the individual’s sociability by observing the interactions between conspecifics (22): a focal fish was placed in a central compartment (30×15×10 cm) of a three-compartment tank, separated by transparent and sealed partitions. A shoal of fish was placed in one of the lateral compartments (15×10×10 cm), while the other contained only water.…”

“…10 min retention) social memory was adapted from the procedure already developed in our lab for long-term (i.e. 24h retention) social memory in zebrafish (31), and has already been used successfully in a previous study (22). A focal fish was placed for 10 min in the central compartment of a three-compartment tank, separated by transparent and sealed partitions, to acclimatize.…”

Advances in neurohypophysial hormones research

“…Exemplarily, Tsuji and colleagues demonstrate that changes in OXT‐ergic signalling components are associated with this behavioural deficiency and identify a critical early postnatal developmental period, in which administration of OXT increases the call rate of valproic acid‐treated pups 9 . Another study by Ribeiro and colleagues uses the zebrafish, an emerging animal model of social behaviour, to demonstrate that OXT signalling differentially regulates social modalities 10 . They find that mutant zebrafish lacking a functional OXT receptor display normal drive to approach conspecifics, whereas their ability to discriminate between novel and familiar fish is impaired.…”