Aggressive behavior in mice is encoded by a distributed brain network (EN-AggINH) that actively inhibits aggression through synchronized theta and beta oscillations relaying through medial prefrontal cortex, and precision editing of a key medial prefrontal cortex-to-nucleus accumbens circuit within this network chronically suppresses violent action while preserving non-aggressive social behaviors.

Aggression is a psychological state characterized by intent to harm oneself or others, and often manifests as hostile, harmful, or violent action. Social aggression can aid an organism in securing access to resources, or it can impair group function and survival in behavioral pathology. Since many brain regions contribute to multiple social behaviors, expanded knowledge of how the brain distinguishes between social states would enable the development of interventions that suppress violent action, while leaving other social behaviors intact. Here we showed that a murine aggressive internal state is encoded by a widespread network. This network is organized by prominent and synchronized theta (4-11 Hz) and beta (14-30 Hz) oscillations that relay through the medial prefrontal cortex, and couples to widespread cellular firing. Strikingly, network activity during social isolation was found to encode the trait aggressiveness of mice, and causal cellular manipulations known to impact aggression were found to modulate the network’s activity. We next established that this network mediates aggression using closed-loop stimulation of medial prefrontal cortex and causal mediation analysis. Finally, we deployed ‘Long-term integration of Circuits using connexins’ (LinCx) to selectively edit a key circuit within the network from the medial prefrontal cortex to nucleus accumbens. Editing this circuit chronically suppressed violent action while leaving non-aggressive social behavior intact.