Anatomical and Functional Characterization of Central Amygdala Glucagon-Like Peptide 1 Receptor Expressing Neurons

Abstract

Glucagon-like peptide 1 receptors (GLP-1Rs) are highly expressed in the brain and are responsible for mediating the acute anorexigenic actions of widely prescribed GLP-1R agonists. Neurobiological efforts to localize the hypophagic effects of GLP-1R agonists in the brain have mainly focused on the hypothalamus and hindbrain. In this study, we performed a deep anatomical and neurophysiological characterization of GLP-1Rs in the central nucleus of the amygdala (CeA). At an mRNA level, we found that Glp1r is diffusely coexpressed in known CeA subpopulations like protein kinase c δ (Prkcd), somatostatin (Sst), or tachykinin2 (Tac2). At a cellular level, we used Glp1r-Cre mice and viral Cre-dependent tracing to map the anatomical positions of GLP-1R cells across the rostral-caudal axis of the CeA and in CeA subdivisions. We found that Glp1rCeA cells are highly enriched in the medial subdivision of the CeA (CeM). Using whole cell patch clamp electrophysiology, we found that Glp1rCeA neurons are characterized by the presence of Ih-like currents and resemble a low threshold bursting neuronal subtype in response to hyperpolarizing and depolarizing current injections. We observed sex differences in the magnitude of Ih-like currents and membrane capacitance. At rest, we observed that nearly half of Glp1rCeA neurons are spontaneously active. We observed that active and inactive neurons display significant differences in excitability even when normalized to an identical holding potential. Our data are the first to deeply characterize the pattern of Glp1r in the CeA and study the neurophysiological characteristics of CeA neurons expressing Glp1r. Future studies leveraging these data will be important to understanding the impact of GLP-1R agonists on feeding and motivation.

Glucagon-like peptide-1 receptors in the gustatory cortex influence food intake

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Projections from infralimbic medial prefrontal cortex glutamatergic outputs to amygdala mediates opioid induced hyperalgesia in male rats

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Activity of brain stem glucagon neurons are modulated by energy state and encode sex and frequency-dependent negative valence and anxiety

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“…1B, C). To better understand our published Gcg-iCre mouse line 56 ; we performed fluorescence in situ hybridization and quantified Gcg and iCre mRNA in the NTS (FIG. 1D-I).…”