Constructing the habituome for phenotype-driven zebrafish research

Intra-session habituation to novelty reflects spatial working memory (related to exploration and cognition), and is observed in various species, including zebrafish (Danio rerio). With the growing understanding of complex zebrafish behaviors, the extent to which they habituate remains unclear. Here we perform a large-scale characterization of zebrafish novelty-evoked (novel tank and open field) behaviors, to establish their grouping based on intra-session habituation and sensitivity to anxiolytic or anxiogenic manipulations. We also assess multiple behaviors in high- and low-anxiety sub-cohorts of a large heterogeneous zebrafish population, comparing their habituation profiles. Overall, our analyses demonstrate that anxiety responsivity and the ability to habituate show little correlation for multiple zebrafish behaviors, suggesting that they most likely represent distinct behavioral phenomena in novel environments. Using these data, we also present the habituome - a new conceptual approach to study affective and cognitive responses in zebrafish by examining a big set of their habituation phenotypes. Given marked similarity in animal novelty exploration, this approach may also be used to construct habituomes in other model organisms, including rodents and humans.