Figure 1.

Inhibition of dLS^GLP−1Rneurons acutely increases food intake.

(A) Brain schematic of viral injection for chemogenetic dLS^GLP−1R neurons inhibition.

(B) Transduction of dLS^GLP−1R neurons with hM4Di-mCherry.

(C) CNO application hyperpolarized the resting membrane potential and reduced the firing rate of dLS^GLP−1R neurons (paired t-test, t(12) = 6.281, p < 0.0001, n = 12 cells from 3 mice).

(D–F) Chemogenetic inhibition of dLS^GLP−1R neurons increased food intake (D) during the dark cycle when fed (two-way ANOVA, main effect of Group: F(1,120) = 14.44,p = 0.0002; main effect of time: F(4,120) = 71.72, p < 0.0001, no interaction between Group and Time: F (4,120) = 1.691, p = 0.1566), (E) during the light cycle when fed (two-way ANOVA, main effect of Group: F(1,120) = 53.89, p < 0.0001; main effect of time: F(4,120) = 58.53, p <0.0001, interaction between Group and Time: F(4,120) = 4.284, p = 0.0028) and (F) refeeding following an overnight fast (two-way ANOVA, main effect of Group: F(1,120) = 28.55, p < 0.0001; main effect of Time: F(4,120) = 68.25, p < 0.0001, interaction between Group and Time: F(4,120) = 2.463, p = 0.0488). n = 13 mice per group.

Data are presented as mean ± SEM. Sidak's multiple comparisons test: ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.