Elsevier

Molecular Metabolism

Volume 4, Issue 10, October 2015, Pages 718-731
Molecular Metabolism

Original article
Distribution and characterisation of Glucagon-like peptide-1 receptor expressing cells in the mouse brain

https://doi.org/10.1016/j.molmet.2015.07.008Get rights and content
Under a Creative Commons license
open access

Highlights

  • This transgenic mouse allows accurate evaluation of the distribution of GLP-1 receptor expressing cells.

  • GLP-1 depolarises PVN, BNST and hippocampus neurons.

  • GLP-1R expressing cells can be manipulated in vivo using this transgenic mouse.

Abstract

Objective

Although Glucagon-like peptide 1 is a key regulator of energy metabolism and food intake, the precise location of GLP-1 receptors and the physiological relevance of certain populations is debatable. This study investigated the novel GLP-1R-Cre mouse as a functional tool to address this question.

Methods

Mice expressing Cre-recombinase under the Glp1r promoter were crossed with either a ROSA26 eYFP or tdRFP reporter strain to identify GLP-1R expressing cells. Patch-clamp recordings were performed on tdRFP-positive neurons in acute coronal brain slices from adult mice and selective targeting of GLP-1R cells in vivo was achieved using viral gene delivery.

Results

Large numbers of eYFP or tdRFP immunoreactive cells were found in the circumventricular organs, amygdala, hypothalamic nuclei and the ventrolateral medulla. Smaller numbers were observed in the nucleus of the solitary tract and the thalamic paraventricular nucleus. However, tdRFP positive neurons were also found in areas without preproglucagon-neuronal projections like hippocampus and cortex. GLP-1R cells were not immunoreactive for GFAP or parvalbumin although some were catecholaminergic. GLP-1R expression was confirmed in whole-cell recordings from BNST, hippocampus and PVN, where 100 nM GLP-1 elicited a reversible inward current or depolarisation. Additionally, a unilateral stereotaxic injection of a cre-dependent AAV into the PVN demonstrated that tdRFP-positive cells express cre-recombinase facilitating virally-mediated eYFP expression.

Conclusions

This study is a comprehensive description and phenotypic analysis of GLP-1R expression in the mouse CNS. We demonstrate the power of combining the GLP-1R-CRE mouse with a virus to generate a selective molecular handle enabling future in vivo investigation as to their physiological importance.

Keywords

Glucagon-like peptide-1 receptor
Electrophysiology
Channelrhodopsin
Preproglucagon
GLP-1
PPG

Abbreviations

AP
area postrema
BNST
bed nucleus stria terminalis
DMH
dorsomedial nucleus of the hypothalamus
DMV
dorsal motor nucleus of the vagus
Ex-4
Exendin-4
GFAP
glial fibrillary acidic protein
GFP
green fluorescent protein
GLP-1
Glucagon-like peptide-1
GLP-1R
Glucagon-like peptide-1 receptor
NAc
nucleus accumbens
NTS
nucleus of the solitary tract
PARV
parvalbumin
PPG
preproglucagon
PVN
paraventricular nucleus of the hypothalamus
TH
tyrosine hydroxylase
VTA
ventral tegmental area
YFP
yellow fluorescent protein

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