Extended Data Fig. 4: Neural activity in the aDCN suppresses food intake independent of hunger state with no compensatory metabolic changes.
From: Reverse-translational identification of a cerebellar satiation network
(a) Experimental design: meal pattern measurements of 24-h food-deprived mice following vehicle or CNO i.p. administration. (b) Latency to first bite in food-deprived mice with hM3D(Gq) expression in the aDCN-LAT (n = 9), aDCN-INT (n = 16) or mCherry control in the aDCN (n = 8) following vehicle or CNO treatment (two-way ANOVA interaction P < 0.001, main effect P = 0.005; Holm-Sidak’s, P < 0.001). (c) Average meal duration during a 1-h chow intake assay following 24-h food deprivation in mice with hM3D(Gq) expression in the aDCN-LAT (n = 9), aDCN-INT (n = 16 mice), or control mCherry expression in the aDCN (n = 8) following vehicle or CNO treatment (two-way ANOVA interaction P = 0.005, main effect P < 0.001; Holm-Sidak’s, P < 0.001). (d) Rate of food intake during a 1-h chow intake assay following 24-h food deprivation in mice with hM3D expression in the aDCN-LAT (n = 9), aDCN-INT (n = 16), or control mCherry expression in the aDCN (n = 8) following vehicle or CNO treatment (two-way ANOVA interaction P = 0.748). (e) Experimental design: meal pattern measurements of ad libitum fed mice following vehicle or CNO i.p. administration. (f) Chow intake in ad libitum fed mice with hM3D(Gq) expression following vehicle or CNO treatment (aDCN-LAT: n = 9, aDCN-INT: n = 16, mCherry control: n = 8; two-way ANOVA, interaction P = 0.001, main effect P = 0.006; Holm-Sidak’s, P < 0.001). (g) Latency to first bite in ad libitum fed mice with hM3D(Gq) expression following vehicle or CNO treatment (aDCN-LAT: n = 9, aDCN-INT: n = 16, mCherry control: n = 8; two-way ANOVA interaction P < 0.001, main effect P < 0.001; Holm-Sidak’s, P<0.001). (h) Chow intake in ad libitum fed mice with mCherry control or hM3D(Gq) expression in the pDCN following vehicle or CNO treatment (pDCN mCherry: n = 8, pDCN hM3D(Gq): n = 12; two-way ANOVA interaction P=0.358). (i) Schematic of the metabolic monitoring experiment. (j) Energy expenditure (kcal) over a 48-h period in mice with mCherry control (n = 8) or hM3D(Gq) (n = 7) expression in the aDCN-LAT (unpaired t-test, P = 0.004). (k) Energy intake (EI) and energy expenditure (EE) over 48-h period in mice with mCherry control or hM3D(Gq) expression in the aDCN-LAT following CNO treatment normalized to vehicle treatment (n = 7 control, 8 aDCN-LAT-hM3D(Gq), repeated measures two-way ANOVA interaction P < 0.001, main effect P<0.001; Holm-Sidak’s, P < 0.001, P = 0.009 (EE); P<0.001, P < 0.001, P < 0.001, P = 0.006 (EI)). Data are expressed as mean ± SEM, two-sided P values, t-tests and post-hoc comparisons: **P<0.01, ***P < 0.001, ANOVA interaction: ∞∞∞P < 0.01, ∞∞∞P<0.001; ANOVA main effect of group: ¤¤P < 0.01, ¤¤¤P<0.001. Statistical analysis in Supplementary Table 1
