Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.
bioRxiv
; 2024 Mar 27.
Article
in En
| MEDLINE
| ID: mdl-38585874
ABSTRACT
Objective:
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; dLS GLP-1R ) and their downstream projections on food intake and determine the relationship with feeding regulation.Methods:
Using chemogenetic manipulations, we assessed how activation or inhibition of dLS GLP-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 dLS GLP-1R neurons to the lateral hypothalamic area (LHA) in regulating food intake.Results:
Chemogenetic inhibition of dLS GLP-1R neurons increases food intake. LHA is a major downstream target of dLS GLP-1R neurons. The dLS GLP-1R âLHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLS GLP-1R âLHA projections modestly decreases food intake, optogenetic stimulation of the dLS GLP-1R âLHA projection terminals in the LHA rapidly suppressed feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLS GLP-1R âLHA GABA release.Conclusions:
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. Highlights Chemogenetic inhibition of dLS GLP-1R neurons boosts food intake in mice dLS GLP-1R neuron activation does not alter feeding, likely by collateral inhibition dLS GLP-1R neurons project to LHA and release GABA Activation of dLS GLP-1R âLHA axonal terminals suppresses food intake GLP-1R agonism enhances dLS GLP-1R âLHA GABA release via a presynaptic mechanism.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
BioRxiv
Year:
2024
Document type:
Article