A PVH-to-parabrachial BDNF circuit mediates non-aversive feeding suppression

SUMMARY Parabrachial nucleus (PBN) CGRP neurons mediate aversive feeding suppression, but PBN circuitry governing homeostatic, non-aversive feeding suppression remains poorly understood. Here, we identify a circuit in which paraventricular hypothalamus (PVH) neurons innervate BDNF-expressing ventrolateral/dorsolateral PBN (vl/dlPBN BDNF ) neurons, which project to multiple hypothalamic nuclei. Refeeding strengthens excitatory and weakens inhibitory synaptic transmission in LPBN-projecting PVH neurons and preferentially induced Bdnf and Fos in vl/dlPBN BDNF neurons compared with elPBN CGRP neurons, whereas noxious LPS preferentially activated elPBN CGRP neurons. Gain- and loss-of-function experiments demonstrated that vl/dlPBN BDNF neurons are sufficient and necessary for feeding suppression without inducing conditioned taste aversion and that this effect require BDNF-TrkB signaling. In addition to hypothalamic inputs, vl/dlPBN BDNF neurons receive dense inputs from major downstream targets of elPBN CGRP neurons. Thus, vl/dlPBN BDNF neurons define a non-aversive feeding-suppression circuit positioned to integrate hypothalamic homeostatic signals with aversive signals, thereby coordinating food intake with internal energy needs and potentially harmful physiological conditions.