Social isolation is associated with microRNA expression changes in the visual system of poison frog tadpoles

Abstract

Brain microRNA (miRNA) expression can shift in response to the social environment, translating external cues into regulatory action that can influence brain structure, neural activity, and behavior. miRNAs are key drivers of behavioral flexibility, regulating gene networks involved in neuroplasticity. We manipulated social rearing conditions of brilliant-thighed poison frog tadpoles (Allobates femoralis) to test whether isolation-linked behavioral changes are associated with altered miRNA expression in the midbrain and eyes, tissues linked by the retinotectal tract, a known connection for trafficked precursor miRNAs. We asked whether isolation alters visually guided behavior using a light/dark preference assay and found that isolated tadpoles spent less of the trial on the dark side than did group-housed tadpoles. In a social place preference assay, group-housed tadpoles preferred a zone near a conspecific over an object control when provided with multimodal sensory access, but not when access was restricted to vision alone. We next tested whether social rearing conditions influenced miRNA expression and found that isolated tadpoles exhibited upregulation of miR-15-P1c_3p*, the canonically non-dominant arm of an understudied miRNA, in the midbrain and eyes. We detected a shift in arm dosing for miR-124, a miRNA with conserved roles in neural differentiation and plasticity. Finally, social isolation during development was associated with downregulation of parathyroid hormone 2 (pth2), a peptide associated with social isolation and mechanosensation in other aquatic larvae. This work contributes to a growing body of literature implicating miRNAs in developmental neuroplasticity, presenting precedented and novel signatures of the transcriptional and regulatory response to isolation.