| Summary: | Social learning plays important roles in gaining new foraging skills and food preferences. However, the potential role and molecular mechanism of social learning in acquiring new feeding habits is less clear in fish. In the present study, we examined the success rate of feeding habit domestication from live prey fish to dead prey fish, as well as the food intake of dead prey fish in mandarin fish with or without feeders of dead prey fish as demonstrators. Here, we found that mandarin fish can learn from each other how to solve novel foraging tasks, feeding on dead prey fish. In addition, the analysis of gene expressions and signaling pathways of learning through Western blotting and transcriptome sequencing shows that the expression of the <i>c-fos, fra2, zif268, c/ebpd</i> and <i>sytIV</i> genes were significantly increased, and the anorexigenic <i>pomc</i> and <i>leptin a</i> expressions were decreased in fish of the learning group. The phosphorylation levels of protein kinase A (PKA) and Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII) in the learning group were significantly higher than those of the control group, while the phosphorylation level of S6 ribosomal protein (S6) was lower. With the inhibitors of PKA and CaMKII signaling and the chromatin immunoprecipitation (ChIP) assay, we further found that the social learning of new feeding habits in mandarin fish could be attributed to the activation of the CaMKII signaling pathway and then the stimulation of the expression of the <i>c-fos</i> gene, which might be an important transcriptional factor to inhibit the expression of the anorexigenic gene <i>pomc</i>, resulting in the food intake of dead prey fish in mandarin fish. Altogether, our results support the hypothesis that social learning could facilitate the acquisition of novel feeding habits in fish, and it considerably increases the rate of subsequent individual food intake and domestication through the interaction between the learning gene <i>c-fos</i> and the appetite control gene <i>pomc</i>.
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