Fig. 2: ENS responses to mucosal nutrient perfusion.

a,d,g,m,p,s, Mucosal perfusion of glucose (a,m), acetate (d,p) or l-Phe (g,s) activates a subset of enteric neurons (arrowheads). Nutrients were applied at t = 10–40 s. b,e,h, Top, submucosal responders (green) to glucose (b), acetate (e) or l-Phe (h). Middle, submucosal ganglia were labelled for ChAT and VIP. Bottom, overlays demonstrate that submucosal responders were cholinergic. n,q,t, Top, myenteric responders (cyan) to glucose (n), acetate (q) or l-Phe (t). Middle, myenteric ganglia were labelled for calbindin and nNOS. Bottom, myenteric responders included calbindin⁺ and nNOS⁺ neurons. c,f,i, Ca²⁺ transients in submucosal responders to glucose (c), acetate (f) or l-Phe (i). o,r,u, Ca²⁺ transients in myenteric responders to glucose (o), acetate (r) or l-Phe (u). j, The percentage of submucosal neurons that responded to mucosal high K⁺ (muc hK⁺), glucose, acetate and l-Phe was comparable. n = 5–10 fields of view (FOVs) imaged. k, Submucosal responders were predominantly cholinergic. l, The cell diameter of responders was comparable between nutrients (ChAT⁺, black; VIP⁺, cyan). A difference was detected between muc hK⁺ and l-Phe responders (*P = 0.039; one-way analysis of variance (ANOVA), Tukey’s multiple comparisons test). n = 4–6 preparations. v, The percentage of myenteric responders to muc hK⁺, glucose and acetate was comparable. l-Phe evoked a smaller response than muc hK⁺ (*P = 0.0334; one-way ANOVA, Tukey’s multiple comparisons test). n = 5–10 FOVs imaged. w, Many myenteric responders were calbindin⁺. x, The cell diameter of myenteric responders differed between stimuli (*P < 0.05, **** P < 0.0001; one-way ANOVA, Tukey’s multiple comparisons test; calbindin⁺, black; nNOS⁺, green; calbindin⁻nNOS⁻, blue). n = 4–7 preparations. Data are mean ± s.e.m. Scale bars, 20 µm. Drawings at the top are adapted from ref. ³⁰ (Wiley).

Source Data