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

  • Smith MA Institute of Clinical Sciences, Faculty of Medicine, Imperial College, London, United Kingdom.
  • Choudhury AI MRC London Institute of Medical Sciences, London, United Kingdom.
  • Glegola JA MRC London Institute of Medical Sciences, London, United Kingdom.
  • Viskaitis P MRC London Institute of Medical Sciences, London, United Kingdom.
  • Irvine EE MRC London Institute of Medical Sciences, London, United Kingdom.
  • de Campos Silva PCC MRC London Institute of Medical Sciences, London, United Kingdom.
  • Khadayate S MRC London Institute of Medical Sciences, London, United Kingdom.
  • Zeilhofer HU Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
  • Withers DJ Institute of Clinical Sciences, Faculty of Medicine, Imperial College, London, United Kingdom.
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  • 2019-09-27
Published in:
  • The Journal of clinical investigation. - 2020
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
English 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.
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  • English
Open access status
hybrid
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Persistent URL
https://folia.unifr.ch/global/documents/258426
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