A limbic circuit selectively links active escape to food suppression

Stress has pleiotropic physiologic effects, but the neural circuits linking stress to these responses are not well understood. Here, we describe a novel population of lateral septum neurons expressing neurotensin (LS^Nts) in mice that are selectively tuned to specific types of stress. LS^Nts neurons increase their activity during active escape, responding to stress when flight is a viable option, but not when associated with freezing or immobility. Chemogenetic activation of LS^Nts neurons decreases food intake and body weight, without altering locomotion and anxiety. LS^Nts neurons co-express several molecules including Glp1r (glucagon-like peptide one receptor) and manipulations of Glp1r signaling in the LS recapitulates the behavioral effects of LS^Nts activation. Activation of LS^Nts terminals in the lateral hypothalamus (LH) also decreases food intake. These results show that LS^Nts neurons are selectively tuned to active escape stress and can reduce food consumption via effects on hypothalamic pathways.