Population coding of predator imminence in the hypothalamus

Hypothalamic VMHdm SF1 neurons are activated by predator cues and are necessary and sufficient for instinctive defensive responses. However, such data do not distinguish which features of a predator encounter are encoded by VMHdm SF1 neural activity. To address this issue, we imaged VMHdm SF1 neurons at single-cell resolution in freely behaving mice exposed to a natural predator in varying contexts. Our results reveal that VMHdm SF1 neurons do not represent different defensive behaviors, but rather encode predator identity and multiple predator-evoked internal states, including threat-evoked fear/anxiety; neophobia or arousal; predator imminence; and safety. Notably, threat and safety are encoded bi-directionally by anti-correlated subpopulations. Finally, individual differences in predator defensiveness are correlated with differences in VMHdm SF1 response dynamics. Thus, different threat-related internal state variables are encoded by distinct neuronal subpopulations within a genetically defined, anatomically restricted hypothalamic cell class. Highlights Distinct subsets of VMHdm SF1 neurons encode multiple predator-evoked internal states. Anti-correlated subsets encode safety vs. threat in a bi-directional manner A population code for predator imminence is identified using a novel assay VMHdm SF1 dynamics correlate with individual variation in predator defensiveness.