Proopiomelanocortin (POMC) is a negative regulator of tadpole aggression through opioid receptor signaling

Aggression is a common behavioral response to limited environmental resources. Most research on the neural basis of aggression in vertebrates focuses on adult males, where sex steroid hormones and the ventromedial hypothalamus are important regulators of aggressive behavior. However, the young of many species also display aggression, although the neural basis of juvenile aggression is not well understood. Here we examine juvenile aggression in Mimic poison frog (Ranitomeya imitator) tadpoles, who live in small isolated pools with limited resources and display aggressive behaviors towards intruder tadpoles. We first conducted a longitudinal study of dyadic behavior and found aggressive behavior increases with tadpole age. We next evaluated which brain regions may be important for tadpole aggression by quantifying pS6-positive cells as a proxy for neural activity. We found more pS6-positive cells in the ventral hypothalamus of aggressive tadpoles compared to controls, similar to findings in adult mammals. We then quantified colocalization of pS6 with vasopressin and oxytocin cells and found no difference across behavior groups. Based on this information, we hypothesized that similar brain regions, but different neuromodulators, may promote aggression in juvenile tadpoles compared to the literature in adult animals. We then used an untargeted approach to molecularly profile pS6-positive neurons and found enrichment of the proopiomelanocortin (POMC) gene in aggressive tadpoles. As POMC is cleaved into several signaling peptides, we used pharmacology to target each pathway and discovered that blocking opioid receptors increases aggressive behavior. Together, this work suggests that POMC-derived B-endorphin is a negative regulator of juvenile aggression through the opioid receptor signaling. More broadly, this work suggests that similar brain regions, but different signaling molecules may be used to regulate aggression in adult and juvenile animals.