Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior

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130340-JCI-RG-RV-3_ms_373974.pdfAccepted version12.75 MBAdobe PDFView/Open
130340-JCI-RG-RV-3_sd_373979.pdfSupporting information6.07 MBAdobe PDFView/Open
Title: Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior
Authors: Smith, MA
Choudhury, AI
Glegola, JA
Viskaitis, P
Irvine, EE
Caldas Custodio de Campos Silva, P
Khadayate, S
Zeilhofer, HU
Withers, DJ
Item Type: Journal Article
Abstract: 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. 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 nociceptin/GABAergic neurons may act as a gateway to feeding behavior by connecting AgRP neurons to both homeostatic and non-homeostatic neuronal inputs.
Issue Date: 26-Sep-2019
Date of Acceptance: 1-Sep-2019
URI: http://hdl.handle.net/10044/1/73651
DOI: https://doi.org/10.1172/JCI130340
ISSN: 0021-9738
Publisher: American Society for Clinical Investigation
Journal / Book Title: Journal of Clinical Investigation
Copyright Statement: © 2019 American Society for Clinical Investigation.
Sponsor/Funder: Medical Research Council
Funder's Grant Number: MC-A654-5QB40
Keywords: Immunology
11 Medical and Health Sciences
Publication Status: Published online
Online Publication Date: 2019-09-26
Appears in Collections:Clinical Sciences
Molecular Sciences



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