Extended Data Fig. 9: Impact of optogenetic activation of PVNGLP-1R projections in the DVC on food intake and aversion.
From: State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis
a. Quantification of fasted-refeeding normalized chow intake for ChR2/EYFP mice (normalized to EYFP/ChR2 off average chow intake, 470 nm 20 Hz, 1 s on, 0.5 s off; two-tailed Mann-Whitney test, p = 0.0146, EYFP n = 6 mice, ChR2 n = 7 mice). b. Experimental paradigm for testing sucrose licking in mouse in a head-fixed format. Animals were injected with AAV-ChR2 or EYFP into the PVN, and fiber optics were implanted in the DVC. c. Quantification of body weight changes after 12 weeks of HFD-DIO (two-tailed paired t-test, t(13) = 4.257, p = 0.0011; EYFP n = 6 mice, ChR2 n = 7 mice). d. Raster plots of licks (consumption of 10% sucrose) of energy-replete (fed) ChR2 and EYFP mice (post 12 weeks HFD) after pre (5 min), during blue light photostimulation (470 nm 20 Hz, 1 s on, 0.5 s off, 5 min), and 5 min post optogenetic stimulation. e. Normalized sucrose licking rates before, during and after optogenetic activation (two-way ANOVA, Group effect: F (3, 22) = 1.335e + 017, p < 0.0001; Time effect: F (1.294, 28.47) = 13.27, p = 0.0005; interaction between Group and Time: F (6, 44) = 0.5878, p = 0.7381; Sidak’s multiple comparisons test vs. EYFP Light On ChR2 p = 0.0003; EYFP n = 6 mice, ChR2 n = 7 mice). f. Representative heatmaps depicting the time spent in the real-time place preference task. The colorbar denotes time spent in an area normalized to the maximum time spent. g. Preference of EYFP and ChR2 mice for the photostimulation chamber (470 nm, 20 Hz) (two-tailed Mann-Whitney test, p = 0.9452; EYFP n = 6 mice, ChR2 n = 7 mice). Data are presented as mean ± SEM. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. Illustration in b adapted from SciDraw under a Creative Commons license CC BY 4.0.
