{Reference Type}: Journal Article
{Title}: Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.
{Author}: Lu Y;Wang L;Luo F;Savani R;Rossi MA;Pang ZP;
{Journal}: Mol Metab
{Volume}: 85
{Issue}: 0
{Year}: 2024 Jul 17
{Factor}: 8.568
{DOI}: 10.1016/j.molmet.2024.101960
{Abstract}: <B>OBJECTIVE: </B>Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral septum (dLS; dLSGLP-1R) that project to the lateral hypothalamic area (LHA) on food intake and determine the relationship with feeding regulation.<BR><B>METHODS: </B>Using chemogenetic manipulations, we assessed how activation or inhibition of dLSGLP-1R neurons affected food intake in Glp1r-ires-Cre mice. Then, we used channelrhodopsin-assisted circuit mapping, chemogenetics, and electrophysiological recordings to identify and assess the role of the pathway from dLSGLP-1R →LHA projections in regulating food intake.<BR><B>RESULTS: </B>Chemogenetic inhibition of dLSGLP-1R neurons increases food intake. LHA is a major downstream target of dLSGLP-1R neurons. The dLSGLP-1R→LHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLSGLP-1R→LHA projections modestly decreases food intake, optogenetic stimulation of the dLSGLP-1R→LHA projection terminals in the LHA rapidly suppresses feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLSGLP-1R →LHA GABA release.<BR><B>CONCLUSIONS: </B>Together, these results demonstrate that dLS-GLP-1R neurons and the inhibitory pathway to LHA can regulate feeding behavior, which might serve as a potential therapeutic target for the treatment of eating disorders or obesity.