A Substantia Innominata-Midbrain Circuit Controls a General Aggressive Response

While aggressive behaviors are universal and essential for survival, ‘uncontrollable’ and abnormal aggressive behaviors in animals or humans may have severe adverse consequences or social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but how brain circuits govern a general aggressive response remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to several aggression-provoking cues with the graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice. Activation of pSI neurons projecting to the periaqueductal gray (PAG) increased aggressive arousal and robustly initiated/promoted all the types of aggressive behavior examined in an activity level-dependent manner. Inactivation of the pSI circuit largely blocked diverse aggressive behaviors but not mating. By encoding a general aggressive response, the pSI-PAG circuit universally drives multiple aggressive behaviors and may provide a potential target for alleviating human pathological aggression. In Brief Zhu et al. find that the posterior substantia innominata neurons universally drive aggressive behaviors by representing aggressive state and topography of aggression in mice. Highlights pSI neuronal dynamics reflect aggressive state and the topography of aggression The pSI-PAG circuit promotes arousal and elicits thirteen aggressive behaviors The pSI controls various aggressive behaviors in an activity level-dependent manner Inactivation of the pSI circuit blocks diverse aggressive behaviors but not mating