GLP-1 neurons form a local synaptic circuit within the rodent nucleus of the solitary tract

J. Patrick Card, Aaron L. Johnson, Ida J. Llewellyn-Smith, Huiyuan Zheng, Rishi Anand, Daniel I. Brierley, Stefan Trapp, Linda Rinaman

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24 Citations (Scopus)
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Glutamatergic neurons that express pre-proglucagon (PPG) and are immunopositive (+) for glucagon-like peptide-1 (i.e., GLP-1+ neurons) are located within the caudal nucleus of the solitary tract (cNTS) and medullary reticular formation in rats and mice. GLP-1 neurons give rise to an extensive central network in which GLP-1 receptor (GLP-1R) signaling suppresses food intake, attenuates rewarding, increases avoidance, and stimulates stress responses, partly via GLP-1R signaling within the cNTS. In mice, noradrenergic (A2) cNTS neurons express GLP-1R, whereas PPG neurons do not. In this study, confocal microscopy in rats confirmed that prolactin-releasing peptide (PrRP)+ A2 neurons are closely apposed by GLP-1+ axonal varicosities. Surprisingly, GLP-1+ appositions were also observed on dendrites of PPG/GLP-1+ neurons in both species, and electron microscopy in rats revealed that GLP-1+ boutons form asymmetric synaptic contacts with GLP-1+ dendrites. However, RNAscope confirmed that rat GLP-1 neurons do not express GLP-1R mRNA. Similarly, Ca2+ imaging of somatic and dendritic responses in mouse ex vivo slices confirmed that PPG neurons do not respond directly to GLP-1, and a mouse crossbreeding strategy revealed that <1% of PPG neurons co-express GLP-1R. Collectively, these data suggest that GLP-1R signaling pathways modulate the activity of PrRP+ A2 neurons, and also reveal a local “feed-forward” synaptic network among GLP-1 neurons that apparently does not use GLP-1R signaling. This local GLP-1 network may instead use glutamatergic signaling to facilitate dynamic and potentially selective recruitment of GLP-1 neural populations that shape behavioral and physiological responses to internal and external challenges.

Original languageEnglish
Pages (from-to)2149-2164
Number of pages16
JournalJournal of Comparative Neurology
Issue number14
Early online date17 Jul 2018
Publication statusPublished - 1 Oct 2018


  • GABA
  • glutamate
  • local circuit network
  • noradrenergic
  • NTS
  • preproglucagon
  • prolactin-releasing peptide
  • RRID: AB_2314562
  • RRID: AB_300798
  • RRID: AB_518978
  • synapse


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