Independent inhibitory control mechanisms for aggressive motivation and action

Social behaviors often consist of a motivational phase followed by action. Here we show that neurons in the ventromedial hypothalamus ventrolateral area (VMHvl) of mice encode the temporal sequence of aggressive motivation to action. The VMHvl receives local inhibitory input (VMHvl shell) and long-range input from the medial preoptic area (MPO) with functional coupling to neurons with specific temporal profiles. Encoding models reveal that during aggression, VMHvl shell vgat+ activity peaks at the start of an attack, whereas activity from the MPO–VMHvl vgat+ input peaks at specific interaction endpoints. Activation of the MPO–VMHvl vgat+ input promotes and prolongs a low motivation state, whereas activation of VMHvl shell vgat+ results in action-related deficits, acutely terminating attack. Moreover, stimulation of MPO–VMHvl vgat+ input is positively valenced and anxiolytic. Together, these data demonstrate how distinct inhibitory inputs to the hypothalamus can independently gate the motivational and action phases of aggression through a single locus of control.