Precision editing of an aggression-encoding network relay suppresses violent action in mice

Abstract

Aggression is a psychological state characterized by intent to harm oneself or others, and often manifests as hostile, harmful, or violent action. Here we showed that an aggressive internal state in mice is encoded by a widespread brain network. This network is organized by prominent and synchronized electrical oscillations that relay through the medial prefrontal cortex, and network activity is coupled to widespread cellular firing. Strikingly, network activity during social isolation encoded the innate aggressiveness of mice, and causal cellular manipulations known to impact aggression modulated the network's activity. We established that this network mediates aggression using closed-loop stimulation of medial prefrontal cortex and causal mediation analysis. Finally, we applied 'Long-term Integration of Circuits using connexins' (LinCx) to selectively edit a key circuit within the network from the medial prefrontal cortex to the nucleus accumbens. Editing this circuit durably suppressed violent action while leaving non-aggressive social behavior intact.