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 encode different defensive behaviors but rather represent predator identity and multiple predator-evoked internal states, including threat-evoked fear/anxiety, arousal or neophobia, predator imminence, and safety. Notably, threat and safety are encoded bi-directionally by anti-correlated subpopulations. Strikingly, individual differences in predator defensiveness are correlated with individual 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.