Individual paraventricular hypothalamic GLP-1R neurons track ingestion across energy states

Energy homeostasis is tightly regulated to ensure metabolic health in uncertain environments. Neurons expressing the glucagon-like peptide-1 receptor (GLP-1R) contribute to maintaining body weight, but how their activity is regulated according to energy state remains unclear. Here, we investigated the function and cellular dynamics of GLP-1R-expressing neurons of the paraventricular hypothalamus (PVH^GLP-1R) during food consumption, providing strong evidence of their ability to bidirectionally control feeding. Elevating intracellular signaling through 3',5'-cyclic adenosine monophosphate (cAMP), the major pathway downstream of GLP-1R, suppressed feeding. Using two-photon calcium imaging, we observed heterogeneous single-cell responses to ingestion that occurred regardless of energy state or tastant identity. Longitudinal tracking of individual PVH^GLP-1R neurons revealed dynamic shifts in ingestion-responsive activity between satiety states while the overall population activity remained stable. These findings reveal stable yet dynamic changes in network activity patterns between energy states, highlighting avenues for further investigation of the effects of obesity and GLP-1R agonists.