Extended Data Fig. 9: Contribution of spinal and vagal afferents to exercise performance.

a-d, Averaged hourly distance (a, c) and quantifications (b, d) of voluntary wheel activity of mice receiving CCK-SAP injection into the nodose ganglia (a, b) and mice with surgical resection of the celiac/superior mesenteric ganglion (CSMG) (c, d). Insets show representative recording traces. e-j, Kaplan-Meier plots (e, g, j) and quantifications (f, h, i) of distance (e, f), time (g, h), and energy (I, j) spent on treadmills by mice with surgical resection of the CSMG. k, l, Expression of Maoa (k) and dopamine levels in the striatum (l) after exercise of mice with surgical resection of the CSMG. m, Mean dopamine indicator signal in post-exercise Abx-treated mice, with or without capsaicin treatment. n, Correlation of striatal dopamine levels with distance in running wheels of Trpv1^DTA mice, Abx-treated mice, and controls, with or without capsaicin treatment. o, Quantification of calcium imaging of DRG neurons exposed to stool filtrates from Abx-treated mice and controls. p, q, Recording traces (p) and quantification (q) of calcium imaging of DRG neurons exposed to stool filtrates from GF mice and controls. Arrow indicates treatment time. r-u, Recording traces (r), quantification (s), correlation with wheel running (t), and correlation with post-exercise dopamine levels in the striatum (u) of calcium imaging of DRG neurons exposed to stool filtrates from DO mice. Arrow indicates treatment time. v, w, Recording traces of calcium imaging of DRG neurons exposed to stool filtrates from mice treated with different Abx (v) and to individual metabolites (w). Arrow indicates treatment time. x, y, Recording traces (x) and quantification (y) of calcium imaging of DRG neurons exposed to oleoylethanolamide (OEA) or capsaicin. Error bars indicate means ± SEM. * p < 0.05, ** p < 0.01, *** p<0.001, **** p<0.0001. Exact n and p-values are presented in Supplementary Table 2.

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