Zebrafish (Danio rerio) behavioral laterality predicts increased short-term avoidance memory but not stress-reactivity responses

Once considered a uniquely human attribute, behavioral laterality has proven to be ubiquitous among non-human animals, and is associated with several neurophenotypes in rodents and fishes. Zebrafish (Danio rerio) is a versatile vertebrate model system widely used in translational neuropsychiatric research owing to their highly conserved genetic homology, well-characterized physiological responses, and extensive behavioral repertoire. Although spontaneous left- and right-biased responses, and associated behavioral domains (e.g., stress reactivity, aggression, and learning), have previously been observed in other teleost species, no information relating to whether spontaneous motor left–right-bias responses of zebrafish predicts other behavioral domains has been described. Thus, we aimed to investigate the existence and incidence of natural left–right bias in adult zebrafish, exploiting an unconditioned continuous free movement pattern (FMP) Y-maze task, and to explore the relationship of biasedness on performance within different behavioral domains. This included learning about threat cues in a Pavlovian fear conditioning test, and locomotion and anxiety-related behavior in the novel tank diving test. Although laterality did not change locomotion or anxiety-related behaviors, we found that biased animals displayed a different search strategy in the Y-maze, making them easily discernable from their unbiased counterparts, and increased learning associated to fear cues. In conclusion, we showed, for the first time, that zebrafish exhibit a natural manifestation of motor behavioral lateralization which can influence aversive learning responses.