A molecularly distinct cell type in the midbrain regulates intermale aggression behaviors in mice

BACKGROUND The periaqueductal gray (PAG) is a central hub for regulation of aggression, whereas little is known on the circuitry and molecular mechanisms that govern this regulation. We investigate the role of a distinct cell type, Taschykinin 2 -expressing (Tac2+) neurons, located in the dorsomedial PAG (dmPAG), in modulating aggression in mice. METHODS We combined activity mapping, in vivo Ca2+ recording, chemogenetic and pharmacological manipulation, and a viral-based translating ribosome affinity purification (TRAP) profiling using a mouse resident-intruder model. RESULTS We demonstrate that the dmPAGTac2 neurons were exclusively activated by fighting behaviors. Further, we show that activation of the dmPAGTac2 neurons evoked, while inhibition or genetic ablation of the dmPAGTac2 neurons suppressed fighting behaviors. TRAP proofing of dmPAGTac2 neurons revealed that fighting behaviors specifically induced enrichment of serotonin-associated transcripts to the dmPAGTac2 neurons. Last, we validated these findings by selectively delivering pharmacological agents into the dmPAG and reversed the behavioral outcomes induced by chemogenetic manipulation. CONCLUSIONS We identify that the dmPAGTac2 neuron can regulate mouse aggressive behavior and thus suggest a distinct molecular target for the treatment of exacerbated aggressive behavior in populations that exhibit high-level of violence. ### Competing Interest Statement The authors have declared no competing interest.