A hypothalamus–brainstem circuit governs the prioritization of safety over essential needs
Nathalie Krauth, Lara Kristin Sach, Giacomo Sitzia, Christoffer Clemmensen, Ole Kiehn
Abstract
Animals continuously adapt their behavior to balance survival and fulfilling essential needs. This balancing act involves prioritization of safety over the pursuit of other needs. However, the specific deep brain circuits that regulate safety-seeking behaviors in conjunction with motor circuits remain poorly understood. Here, we identify a class of glutamatergic neurons in the mouse lateral hypothalamic area (LHA) that target the midbrain locomotor-promoting pedunculopontine nucleus (PPN). Following activation, this LHA–PPN pathway orchestrates context-dependent locomotion, prioritizing safety-directed movement over other essential needs such as foraging or social contact. Remarkably, the neuronal activity of this circuit correlates directly with safety-seeking behavior. The circuit may respond to both intrinsic and extrinsic cues, having a pivotal role in ensuring survival. Our findings uncover a circuit motif within the lateral hypothalamus that, when recruited, prioritizes critical needs through the recruitment of an appropriate motor action. Animals need to adapt behavior to balance survival with fulfillment of essential needs. Krauth et al. identify neurons in the lateral hypothalamus that, when activated, prioritize survival over other critical needs by triggering an appropriate motor action.