Fosab, but not fosaa, plays important role in learning and memory in fish—insights from zebrafish gene knockout study

<b>Introduction:</b> Learning and memory allow individuals to adapt to their environmental needs and survive. Fish have the ability to solve complex learning tasks, associative learning, and flexible spatial memory. The proto-oncogene fos (<i>c-fos</i>) has been reported to be involved in brain development, learning and memory in mammals. However, whether the c-fos plays a vital role in learning and memory in fish is unclear. <b>Methods:</b> Almost all fish have two paralogues of <i>c-fos</i> named <i>fosaa</i> and <i>fosab</i>. We used CRISPR/Cas9 technology to generate <i>fosaa</i> and <i>fosab</i> knockout zebrafish models. <b>Results:</b> In this study, we discovered the brain weight marked reduction in <i>fosaa</i> ^-/- and <i>fosab</i> ^-/- zebrafish compared with the wild-type (WT) (AB strain) zebrafish. In the T-maze behavioral assay, the <i>fosab</i> ^-/- zebrafish took significantly more than the average time to complete the assigned trial as the increase in the days compared to WT zebrafish, while the <i>fosaa</i> ^-/- zebrafish did not show a notable variance. The average time to complete the trial in <i>fosab</i> ^-/- zebrafish was significantly higher than in WT zebrafish. The relative mRNA expression level of c-<i>jun</i> in <i>fosab</i> ^-/- zebrafish was significantly higher than that in WT zebrafish, while the <i>fosaa</i> ^-/- zebrafish has no discernible trend. Additionally, the phylogenetic and multiple amino acid alignment results indicated that fish <i>fosab</i> has a higher identity with mammals Fos. <b>Discussion:</b> By integrating the above results, we found that <i>fosab</i>, but not fosaa, may possess a learning and memory function in fish. For the first time, we illustrated the role of <i>fosaa</i> and <i>fosab</i> in learning and memory via <i>c-fos</i> knockout in fish, which can provide new insights into environmental adaptation.