Fig. 3: D1- and D2-neurons of the NAc are differentially activated during feeding and running and oppositely regulate the balance between feeding and voluntary running.

A (Top) Experimental timeline for recording of calcium dynamics during feeding. (Bottom) Normalized calcium activity of D1 and D2-neurons during feeding trials (Z score; 12 trials/animal; D1 events=59; D2 events=60) with quantification of the AUC (Two-way RM ANOVA; Group effect F(1, 117) = 7.376, p = 0.0076; Post-hoc D1 vs D2 0s-60s p = 0.0001), average z-score (Two-way RM ANOVA; Group effect F(1, 117) = 5.489, p = 0.0208; Post-hoc D1 vs D2 0s-60s: p = 0.0001), Peak z-score (Two-way RM ANOVA; Interaction F(1, 117) = 31.07, p = 0.0001; Post-hoc D1 vs D2 −40s-0s p = 0.0099; Post-hoc D1 vs D2 0s-60s p = 0.0391) and transient rates (Two-way RM ANOVA; Interaction F(1, 117) = 12.67, p = 0.0005; Post-hoc D1 vs D2 −40s-0s p = 0.0089; Post-hoc D1 vs D2 0s-60s p = 0.0634).B (Top) Experimental timeline for recording of calcium dynamics during running. (Bottom) Normalized calcium activity of D1 and D2-neurons during running trials (Z score; 12 trials/animal; D1 events = 60; D2 events = 59) with quantification of the AUC (Two-way RM ANOVA; Group effect F(1, 117) = 7.219, p = 0.0083; Post-hoc D1 vs D2 0s-60s: p = 0.0001), average z-score (Two-way RM ANOVA; Group effect F(1, 117) = 5.598, p = 0.0196; Post-hoc D1 vs D2 0s-60s: p = 0.0001), Peak z-score and transient rates. For both A and B, D2-cre: n = 5; D1-cre: n = 5; Blue and red bars represent statistical difference to baseline, black bar significant difference between the relative activity of both subpopulations. C–E (C) Experimental design. Normalized chow consumption and wheel running comparing 1-hour pre-CNO and 1-hour post-CNO injection for chemogenetic activation and inhibition of D2-neurons (D; Two-way RM ANOVA; Feeding: Infusion effect F(1, 13) = 20.70, p = 0.0005; Running: Virus effect F(1, 13) = 25.27, p = 0.0002; Interaction F(1, 13) = 48.01, p = 0.0001; Post-hoc D2Gi vs D2Gq Post infusion p = 0.0001; Post-hoc Pre infusion vs Post infusion D2Gi p = 0.0016 D2Gq p = 0.0002) and D1-neurons (E; Two-way RM ANOVA; Feeding: Virus effect F(1, 14) = 9.012, p = 0.0095; Interaction F(1, 14) = 8.166, p = 0.0127; Post-hoc D1Gi vs D1Gq Post infusion p = 0.0006; Post-hoc Pre infusion vs Post infusion D1Gq p = 0.0495; Running: Virus effect F(1, 14) = 7.508, p = 0.0160; Interaction F(1, 14) = 15.14, p = 0.0016; Post-hoc D1Gi vs D1Gq Post infusion p = 0.0001; Post-hoc Pre infusion vs Post infusion D1Gq p = 0.0072). D2-cre: DREADD Gi n = 7, DREADD Gq n = 7; D1-cre: DREADD Gi n = 8, DREADD Gq 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.