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.