A distinct parabrachial–to–lateral hypothalamus circuit for motivational suppression of feeding by nociception

The motivation to eat is not only shaped by nutrition but also competed by external stimuli including pain. How the mouse hypothalamus, the feeding regulation center, integrates nociceptive inputs to modulate feeding is unclear. Within the key nociception relay center parabrachial nucleus (PBN), we demonstrated that neurons projecting to the lateral hypothalamus ((LH)PBN) are nociceptive yet distinct from danger-encoding central amygdala–projecting ((CeA)PBN) neurons. Activation of (LH)PBN strongly suppressed feeding by limiting eating frequency and also reduced motivation to work for food reward. Refined approach-avoidance paradigm revealed that suppression of (LH)PBN, but not (CeA)PBN, sustained motivation to obtain food. The effect of (LH)PBN neurons on feeding was reversed by suppressing downstream LH(VGluT2) neurons. Thus, distinct from a circuit for fear and escape responses, (LH)PBN neurons channel nociceptive signals to LH(VGluT2) neurons to suppress motivational drive for feeding. Our study provides a new perspective in understanding feeding regulation by external competing stimuli.