1548-P: Functional and Behavioral Dynamics of GLP-1 Receptors in the Central Amygdala

Introduction: Glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake via multiple brain sites, i.e., hypothalamus, hindbrain, and limbic systems. Peripheral and central administration of GLP-1R agonists activate the central nucleus of the amygdala (CeA), yet the mechanisms mediating this action are understudied. In the present study, in vivo fiber photometry and calcium indicator, GCaMP, in the CeA in freely behaving mice was used to determine the role of GLP-1Rs in modulating neural activity in response to peripheral administration of a GLP-1R agonist. Methods: Fiber photometry Results: Freely behaving mice with fiber optic cannulas implanted in CeA were attached to a fiber photometry system and neural activity recorded in response to intraperitoneal administration of saline, Exendin-4 (5 µg/kg, Ex4, agonist), or Exendin-9 (50 µg/kg, Ex9, antagonist). We found that Ex4 activates CeA neurons, and this effect is blocked by prior administration of Ex9. Conclusion: These measurements from freely behaving mice suggest that CeA GLP-1Rs are potentially mediating changes in neuronal activity when activated by a GLP-1R agonist. Currently, we are assessing the behavioral consequences of inhibiting the neuronal signaling of the CeA and its GLP-1R on feeding behavior. Disclosure M. Duran: None. S. Virkus: None. J.A. Hardaway: None. Funding National Institutes of Diabetes and Digestion and Kidney Disease (K01DK115902, R03DK129561); Dr. Tim Gavey (P30DK079626); Dr. James Hill (P30DK056336)