A hypothalamus–brainstem circuit governs the prioritization of safety over essential needs

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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.
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Funding Information
  • Novo Nordisk Fonden (NNF24SA0088394, NNF15OC0014186, NNF22OC0073778)
  • Lundbeck Foundation (R345-2020-1769)
  • Novo Nordisk Foundation Center for Basic Metabolic Research (International Postdoc Fellowship, NNF23SA0084103, NNF18CC0034900)

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