A Ventromedial Hypothalamic Neuron Subset Encodes a Conspecific-Tuned Behavior State Driving Social Investigation

The VMH ^SF1 neurons encode a predator-orientated internal state that drives innate defensive responses. Although neuroanatomical studies show that male mouse VMH ^SF1 neurons are interconnected with structures in the social behavioral network, how VMH ^SF1 neurons represent stimulus and behaviors under social context remain elusive. To address the question, we employed fiber photometry and miniscope Ca ²⁺ imaging on VMH ^SF1 neurons and found that VMH ^SF1 neurons are strongly responsive to social stimuli with a male-biased sex preference, which requires pheromonal signals and intact BNST-VMH pathway. During social interaction, VMH ^SF1 neurons are highly tuned to investigative yet strongly silenced by consummatory social behaviors. Notably, VMH ^SF1 neurons that encode defensive actions and those encoding social investigation are two distinct subpopulations. Lastly, silencing VMH ^SF1 neurons suppresses social investigation. Altogether, our results suggest the existence of a novel, non-defense driving VMH ^SF1 neurons subset that encodes conspecific social cues with sex-bias and prompts social investigation of male mice.