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Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats

Zheng, H and Stornetta, RL and Agassandian, K and Rinaman, L (2015) Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats. Brain Structure and Function, 220 (5). 3011 - 3022. ISSN 1863-2653

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The expression of a vesicular glutamate transporter (VGLUT) suffices to assign a glutamatergic phenotype to neurons and other secretory cells. For example, intestinal L cells express VGLUT2 and secrete glutamate along with glucagon-like peptide 1 (GLP1). We hypothesized that GLP1-positive neurons within the caudal (visceral) nucleus of the solitary tract (cNST) also are glutamatergic. To test this, the axonal projections of GLP1 and other neurons within the cNST were labeled in rats via iontophoretic delivery of anterograde tracer. Dual immunofluorescence and confocal microscopy was used to visualize tracer-, GLP1-, and VGLUT2-positive fibers within brainstem, hypothalamic, and limbic forebrain nuclei that receive input from the cNST. Electron microscopy was used to confirm GLP1 and VGLUT2 immunolabeling within the same axon varicosities, and fluorescent in situ hybridization was used to examine VGLUT2 mRNA expression by GLP1-positive neurons. Most anterograde tracer-labeled fibers displayed VGLUT2-positive varicosities, providing new evidence that ascending axonal projections from the cNST are primarily glutamatergic. Virtually all GLP1-positive varicosities also were VGLUT2-positive. Electron microscopy confirmed the colocalization of GLP1 and VGLUT2 immunolabeling in axon terminals that formed asymmetric (excitatory-type) synapses with unlabeled dendrites in the hypothalamus. Finally, in situ hybridization confirmed that GLP1-positive cNST neurons express VGLUT2 mRNA. Thus, hindbrain GLP1 neurons in rats are equipped to store glutamate in synaptic vesicles, and likely co-release both glutamate and GLP1 from axon varicosities and terminals in the hypothalamus and other brain regions.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Zheng, H
Stornetta, RL
Agassandian, K
Rinaman, Lrinaman@pitt.eduRINAMAN
Date: 28 September 2015
Date Type: Publication
Journal or Publication Title: Brain Structure and Function
Volume: 220
Number: 5
Page Range: 3011 - 3022
DOI or Unique Handle: 10.1007/s00429-014-0841-6
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Refereed: Yes
ISSN: 1863-2653
PubMed ID: 25012114
Date Deposited: 24 Feb 2016 20:36
Last Modified: 30 Mar 2021 12:55


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