Patrick Card, J;
Johnson, AL;
Llewellyn-Smith, IJ;
Zheng, H;
Anand, R;
Brierley, DI;
Trapp, S;
(2018)
GLP-1 neurons form a local synaptic circuit within the rodent nucleus of the solitary tract.
Journal of Comparative Neurology
, 526
(14)
pp. 2149-2164.
10.1002/cne.24482.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | GLP-1 neurons form a local synaptic circuit within the rodent nucleus of the solitary tract |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/cne.24482 |
| Publisher version: | https://doi.org/10.1002/cne.24482 |
| Language: | English |
| Additional information: | © 2018 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | GABA, glutamate, local circuit network, noradrenergic, NTS, preproglucagon, prolactin-releasing peptide, RRID: AB_2314562, RRID: AB_300798, RRID: AB_518978, synapse |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10054517 |
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