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

The VMHSF1 neurons encode a predator-orientated internal state that drives innate defensive responses. Although neuroanatomical studies show that male mouse VMHSF1 neurons are interconnected with structures in the social behavioral network, how VMHSF1 neurons represent stimulus and behaviors under social context remain elusive. To address the question, we employed fiber photometry and miniscope Ca2+ imaging on VMHSF1 neurons and found that VMHSF1 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, VMHSF1 neurons are highly tuned to investigative yet strongly silenced by consummatory social behaviors. Notably, VMHSF1 neurons that encode defensive actions and those encoding social investigation are two distinct subpopulations. Lastly, silencing VMHSF1 neurons suppresses social investigation. Altogether, our results suggest the existence of a novel, non-defense driving VMHSF1 neurons subset that encodes conspecific social cues with sex-bias and prompts social investigation of male mice. HighlightsO_LIA subset of VMHSF1 neurons exhibit preferential response to social cues C_LIO_LIConspecific sex bias of VMHSF1 neurons requires pheromonal signal and BNST input C_LIO_LISocial-tuned VMHSF1 neurons functionally encode social investigation C_LIO_LIPredator defense and social investigation recruits distinct VMHSF1 subgroups C_LI