Abstract
Aggression is an essential animal behavior for survival, particularly in situations where fighting cannot be avoided. In such situations, the choice of fighting strategy (eg biting, charging, or defending) is critical. Although the molecular bases of fighting and aggressiveness have been previously studied, how genetic, transcriptional, and neurobiological mechanisms contribute to the choice of fighting strategy remains largely unknown. Here, we use two subpopulations of chickens bred for cockfighting that show markedly different fighting strategies: offensive and defensive attack. A genome-wide screen comparing individuals from the two subpopulations indicated a polygenic background and we identified 15 candidate genes, five of which are implicated in neuronal development. Among these, the transcription factor gene FOXP1 was notable. FOXP1 is essential for neuronal development in the brain and has been implicated in the regulation of motor circuits. Transcriptomic analysis of the diencephalon also revealed differential expressions of genes involved in neurodevelopment, as well as in the synthesis and release of neurotransmitters. RNA-sequencing and immunohistochemistry suggested that activation of the indirect pathway of the brain motor circuit promotes the defensive fighting strategy. This was further supported by behavioral pharmacological experiments targeting dopaminergic signaling. Taken together, our results indicate that genomic variation and altered expression of neurodevelopment-related genes underlie differences in fighting strategies, and that the neuroendocrine changes in brain circuits further modulate these behavioral outcomes.