TY - JOUR AU - Smith, Mark A. AU - Choudhury, Agharul I. AU - Glegola, Justyna A. AU - Viskaitis, Paulius AU - Irvine, Elaine E. AU - de Campos Silva, Pedro Caldas Custodio AU - Khadayate, Sanjay AU - Zeilhofer, Hanns Ulrich AU - Withers, Dominic J. T1 - Extrahypothalamic GABAergic nociceptin–expressing neurons regulate AgRP neuron activity to control feeding behavior PY - 2020/01/02/ AB - Arcuate nucleus agouti–related peptide (AgRP) neurons play a central role in feeding and are under complex regulation by both homeostatic hormonal and nutrient signals and hypothalamic neuronal pathways. Feeding may also be influenced by environmental cues, sensory inputs, and other behaviors, implying the involvement of higher brain regions. However, whether such pathways modulate feeding through direct synaptic control of AgRP neuron activity is unknown. Here, we show that nociceptin-expressing neurons in the anterior bed nuclei of the stria terminalis (aBNST) make direct GABAergic inputs onto AgRP neurons. We found that activation of these neurons inhibited AgRP neurons and feeding. The activity of these neurons increased upon food availability, and their ablation resulted in obesity. Furthermore, these neurons received afferent inputs from a range of upstream brain regions as well as hypothalamic nuclei. Therefore, aBNST GABAergic nociceptin neurons may act as a gateway to feeding behavior by connecting AgRP neurons to both homeostatic and nonhomeostatic neuronal inputs. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI130340 VL - 130 IS - 1 UR - https://doi.org/10.1172/JCI130340 SP - 126 EP - 142 PB - The American Society for Clinical Investigation ER -