A hypothalamic pathway that suppresses aggression toward superior opponents

Aggression is costly and requires tight regulation. Here we identify the projection from estrogen receptor alpha-expressing cells in the caudal part of the medial preoptic area (cMPOA Esr1 ) to the ventrolateral part of the ventromedial hypothalamus (VMHvl) as an essential pathway for modulating aggression in male mice. cMPOA Esr1 cells increase activity mainly during male–male interaction, which differs from the female-biased response pattern of rostral MPOA Esr1 (rMPOA Esr1 ) cells. Notably, cMPOA Esr1 cell responses to male opponents correlated with the opponents’ fighting capability, which mice could estimate based on physical traits or learn through physical combats. Inactivating the cMPOA Esr1 –VMHvl pathway increased aggression, whereas activating the pathway suppressed natural intermale aggression. Thus, cMPOA Esr1 is a key population for encoding opponents’ fighting capability—information that could be used to prevent animals from engaging in disadvantageous conflicts with superior opponents by suppressing the activity of VMHvl cells essential for attack behaviors.