Nuclei within the limbic system like the central amygdala (CeA) play a critical role in mediating fear, motivation, reward, and appetitive behavior. Although previous reports demonstrate the presence of the glucagon-like peptide-1 receptor (GLP-1R) in limbic nuclei, how limbic neurons mediate the actions of systemically administrated GLP-1R agonists is unclear. In this study, we investigated the CeA’s response to peripherally administered GLP-1R agonist Exendin-4 (Ex-4) in vivo , and determined the functional requirement of select CeA neuron populations in acute Ex-4 induced hypophagia. Using fiber photometry, we observed that Ex-4 promoted a rapid and lasting activation of CeA neurons that was blocked by pretreatment with the GLP-1R antagonist Exendin-9. We then tested the functional requirement of CeA neuron activation in mediating Ex-4 induced hypophagia of standard grain chow using inhibitory chemogenetics. Chemogenetic inhibition of all CeA neurons significantly suppressed the hypophagic actions of Ex-4. Then using selective mouse Cre-drivers, we found that chemogenetic inhibition of protein kinase c delta (Prkcd CeA ) and GLP-1R ( Glp1r CeA ), but not somatostatin ( Sst CeA ), neurons also attenuates the full hypophagic effect of Ex-4. Having observed that inhibition of Glp1r CeA modestly attenuated Ex-4 induced hypophagia of standard chow, we then tested whether these neurons might mediate Ex-4 suppression of energy-dense, palatable diet. We used intermittent high-fat diet (HFD) access and found that inhibition of Glp1r CeA neurons significantly rescued the reduction of HFD consumption by Ex-4. Collectively, these data demonstrate that the CeA responds to peripherally administered GLP-1R agonists and that multiple CeA neuron populations are required for the complete effect of GLP-1R agonist mediated hypophagia.
Duran et al. (Mon,) studied this question.