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 one 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 intestinal microbiota-driven dopamine level influences social interaction and innate color preference in zebrafish larvae

Gut microbiota influence neurodevelopment of brain and programing of behaviors. However, the mechanism underlining the relationship between shoals' behaviors and intestinal microbiota remain controversial and the roles of neurotransmitters are still unclear. Here we show that, shoaling behavior affected the innate color preference of shoals, indicating that shoals tended to choose a favorable color environment that benefits social contact. Meanwhile, administration of D1-R antagonist disrupted the social interaction which led to the deficits of color preference. More importantly, the altered microbiota caused by an antibiotic OTC decreased the sociability and weakened shoals' color preference. When given a supplement of LGG after OTC exposure, fish exhibited an unexpectedly recovery capability in social cohesion and color preference. Our findings show that dopamine level of brain could mediate both social recognition and color preference, and highlight the pathway of microbial metabolites through the microbiota-gut-brain axis that coordinate the production of dopamine.

Social interaction influences innate color preference of zebrafish shoals

The color discrimination can confer survival advantages by helping animals to find nutritious food and shelter and to avoid predator. Zebrafish as a social species, data on innate color preference in shoals remain controversial and there are limited data for this organism. Here we showed that, when given a choice among two color combinations (R-Y, R-G, Y-G, B-G, B-R, B-Y), shoals of zebrafish exhibited a complex pattern of color preference and the order of RYGB preference was R>Y>G, B>G. By contrast, the individual zebrafish showed marked changes, completely losing their preference for all the tested color combinations. To investigate the role of shoaling behavior in color preference, we selected a D1-receptor antagonist (SCH23390), which could disrupt social preference and decrease social interaction in zebrafish. Interestingly, the shoals that were treated by SCH23390 showed no color preference for all color combinations. Our findings indicate that social interaction is involved in color-driven behavior in zebrafish, and reveal the possible mechanisms that the dopaminergic system may contribute to innate color preference in shoals of zebrafish.

Interactive Effects of Sertraline and Diphenhydramine on Biochemical and Behavioral Responses in Crucian Carp (Carassius auratus)

The ecotoxicity of psychiatric pharmaceuticals to aquatic organisms is being increasingly recognized. However, current ecological studies focus on the effects of individual psychiatric pharmaceuticals, with little attention being given to their combined effects. In this study, the interactive effects of two psychiatric pharmaceuticals, sertraline (SER) and diphenhydramine (DPH), on bioconcentration and biochemical and behavioral responses were investigated in crucian carp (Carassius auratus) after seven days of exposure. DPH was found to increase the accumulation of SER in fish tissues relative to SER-alone exposure. In addition, the mixture of SER and DPH significantly changed the activities of antioxidant enzymes and led to significant increases in malondialdehyde content, relative to SER alone. Concerning the neurotoxicity, relative to SER-alone exposure, brain AChE activity was significantly enhanced in fish following the combined exposure. Regarding behavioral responses, swimming activity and shoaling behavior were significantly altered in co-exposure treatments compared with the SER alone. Moreover, the inhibition effects on the feeding rates were increased in co-exposure treatments compared to SER alone. Collectively, our results suggest that the mixtures of psychiatric pharmaceuticals may pose more severe ecological risks to aquatic organisms compared to these compounds individually.

Cerebral Dopamine Neurotrophic Factor regulates multiple neuronal subtypes and behavior

Cerebral Dopamine Neurotrophic Factor (CDNF) protects dopaminergic neurons against toxic damage in the rodent brain, and is in clinical trials to treat Parkinson’s disease patients. Yet the underlying mechanism is poorly understood. To examine its mode of action and significance, we examined the development of neurotransmitter systems from larval to adult mutant zebrafish lacking cdnf. Although a lack of cdnf did not affect overall brain dopamine levels, dopaminergic neuronal clusters showed significant abnormalities. The number of histamine neurons that surround the dopaminergic neurons was significantly reduced. Expression of tyrosine hydroxylase 2 in the brain was elevated in cdnf mutants throughout their lifespan. There were abnormally few GABA neurons in the hypothalamus in the mutant larvae, and expression of glutamate decarboxylase was reduced throughout the brain. cdnf mutant adults showed a range of behavioral phenotypes, including increased sensitivity to pentylenetetrazole-induced seizures. Shoaling behavior of mutant adults was abnormal, and they did not display social attraction to conspecifics. CDNF plays a profound role in shaping the neurotransmitter circuit structure, seizure susceptibility, and complex behaviors in zebrafish. These findings are informative for dissecting the diverse functions of this poorly understood factor in human conditions related to Parkinson’s disease and complex behaviors

High background risk induces risk allocation rather than generalized neophobia in the fathead minnow

To cope with the heterogeneous nature of predation and the trade-off between predator avoidance and foraging, prey animals have evolved several cognitive rules. One of these is the risk allocation hypothesis, which predicts that in environments with long periods of sustained high risk, individuals should decrease their antipredator effort to satisfy their metabolic requirements. The neophobia hypothesis, in turn, predicts increased avoidance of novel cues in high-risk habitats. Despite the recent interest in predator-induced neophobia across different sensory channels, tests of such generalized neophobia are restricted to a single fish taxon, the Cichlidae. Hence, we retested the generalized neophobia hypothesis in fathead minnows Pimephales promelas, a small schooling North American cyprinid fish. From hatching onward, minnows were exposed to conspecific alarm cues, which indicate predation risk, or distilled water in a split-clutch design. After 1 month, shoaling behavior was examined prior and subsequent to a mechanical predator disturbance. Fish previously exposed to elevated background risk formed compact shoals for a shorter time interval after the stimulus compared with controls. These results contrast previous studies of generalized neophobia but match the risk allocation hypothesis. Consequently, risk allocation and generalized neophobia are not ubiquitous cognitive rules but instead evolved adaptations of different taxa to their respective environments.