Fig. 5: Effect of chronic and simultaneous chemogenetic manipulations of D2-neurons and D1-neurons of the NAc in a wheel-running/high-fat free-feeding choice procedure.

A Schematic design for the transgenic and viral strategy for concomitant chemogenetic manipulation of D1- and D2-neuroins of the NAc (left) and representative pattern of expression of cre-dependent GFP and flp-dependent mCherry in double transgenic D1-FlpxD2-cre mice (right). Scale bar 250 µm. B–D Food consumption over time (B; Two-way RM ANOVA; Interaction F(14, 189) = 7.911, p = 0.0001; Post-hoc WT vs D1Gq-D2Gi: Day1 p = 0.0498, Day24 p = 0.0056, Day25 p = 0.0769; Post-hoc WT vs D1Gi-D2Gq: Day3 p = 0.0648, Day24 p = 0.0967; Post-hoc D1Gi-D2Gq vs D1Gq-D2Gi: Day1 p = 0.0057, Day3 p = 0.0277, Day24 p = 0.0004, Day25 p = 0.0001), variation in wheel running (C; Two-way RM ANOVA; Virus effect F(2, 23) = 8.839 p = 0.0014; Interaction F(34, 376) = 3.486, p = 0.0001; Post-hoc WT vs D1Gq-D2Gi: Day1 p = 0.0791, Day3 p = 0.0122, Day5 p = 0.0013, Day7 p = 0.0148, Day9 p = 0.0105, Day13 p = 0.0106, Day15 p = 0.0164, Day17 p = 0.0059, Day19 p = 0.0010; Post-hoc D1Gi-D2Gq vs WT: Day1 p = 0.0966, Day3 p = 0.0600, Day5 p = 0.0005, Day11 p = 0.0336, Day13 p = 0.0039, Day15 p = 0.0331, Day17 p = 0.0047, Day19 p = 0.0282, Day21 p = 0.0568, Day23 p = 0.0443) and variation in total and fat mass (D; One way ANOVA; Total mass variation CNO period F(2, 27) = 9.421, p = 0.0008; Post-hoc WT vs D1Gi-D2Gq p = 0.0638; Post-hoc D1Gq-D2Gi vs D1Gi-D2Gq p = 0.0006; Fat mass variation CNO period Kruskal-Wallis p = 0.0002; Post-hoc WT vs D1Gq-D2Gi p = 0.0408; Post-hoc D1Gq-D2Gi vs D1Gi-D2Gq p = 0.0001; Total mass variation CNO removal F(2, 27) = 19.79 p = 0.0001; Post-hoc WT vs D1Gi-D2Gq p = 0.0004; Post-hoc D1Gq-D2Gi vs D1Gi-D2Gq p = 0.0001; Fat mass variation CNO removal F(2, 27) = 52.97 p = 0.0001; Post-hoc WT vs D1Gi-D2Gq p = 0.0171; Post-hoc WT vs D1Gq-D2Gi p = 0.0001; Post-hoc D1Gq-D2Gi vs D1Gi-D2Gq p = 0.0001) were measured under chronic manipulations of both subpopulations (D1Gq-D2Gi: concomitant activation of D1-neurons and inhibition of D2-neurons; D1Gi-D2Gq: concomitant inhibition of D1-neurons and activation of D2-neurons) compared to WT controls, as well as after CNO cessation. D1-D2 WT n = 9; D1Gi-D2Gq n = 9, D1Gq-D2Gi n = 8. $: 0.05 < p < 0.1 *: p < 0.05; **: p < 0.01; ***: p < 0.001 Error bars = s.e.m. Detailed statistics are displayed in Supplementary Table 2. Source data are provided as a Source Data file.