Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior
File(s)
Published version
Supporting information
Author(s)
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.
Date Issued
2020-01-02
Date Acceptance
2019-09-19
Citation
Journal of Clinical Investigation, 2020, 130 (1), pp.126-142
ISSN
0021-9738
Publisher
American Society for Clinical Investigation
Start Page
126
End Page
142
Journal / Book Title
Journal of Clinical Investigation
Volume
130
Issue
1
Copyright Statement
© 2020 Smith et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor
Medical Research Council
Identifier
https://www.jci.org/articles/view/130340
Grant Number
MC-A654-5QB40
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
STRIA TERMINALIS
MESSENGER-RNA
BED NUCLEUS
AXONAL PROJECTIONS
RECEPTOR
CIRCUIT
MODULATION
STRESS
ORGANIZATION
SUPPRESSES
Melanocortin
Metabolism
Neuroendocrine regulation
Neuroscience
Obesity
Agouti-Related Protein
Animals
Arcuate Nucleus of Hypothalamus
Body Weight
Feeding Behavior
GABAergic Neurons
Male
Mice
Mice, Inbred C57BL
Neuropeptide Y
Opioid Peptides
Septal Nuclei
Septal Nuclei
Animals
Mice, Inbred C57BL
Mice
Body Weight
Neuropeptide Y
Opioid Peptides
Feeding Behavior
Male
Agouti-Related Protein
GABAergic Neurons
Arcuate Nucleus of Hypothalamus
Immunology
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2019-11-18