Figure 5. Stomach-innervating spinal sensory neurons convey gastric distention signals induced by ileal GLP-1.

(A) Ablation of stomach-innervating DRGs (DRG^Stom). Retrograde Cre-expressing AAVrg-Cre was injected into the stomach of iDTR mice, followed by intrathecal infusions of diphtheria toxin (DTx). DRG^Stom ablation abolished GLP-1ⁱⁱ-induced anorexia, two-way mixed RM-ANOVA, infusate F(2,16) = 29.592, * p < 0.001, group F(1,8) = 17.513, *p = 0.003, infusate × group F(2,16) = 13.117, *p < 0.001.

(B) DRG^Stom ablation significantly attenuated gastric balloon-induced anorexia. (Ba) Chow intake: two-way mixed RM-ANOVA, inflation × group F(1,8) = 2.725, p = 0.137, main effects of balloon F(1,8) = 26.270, *p < 0.001 and group F(1,8) = 39.166, **p < 0.001. (Bb) Normalized intake reduction upon balloon inflation, T(8) = 4.788, *p = 0.001.

(C and D) As in (A) and (B) but ablation of stomach-innervating NGs (NG^Stom). NG^Stom ablation failed to affect either GLP-1ⁱⁱ-induced (C, two-way mixed RM-ANOVA infusate × group F[2,16] = 0.557, p = 0.583), or balloon-induced (Da, two-way mixed RM-ANOVA, inflation 3 group F[1,8] = 2.262, p = 0.171; Db, T[8] = 0.304, p = 0.769) anorexia.

(E) HSV-LSL-TK-Tomato bilaterally injected into DRG^Stom (T7–T10) revealed robust recombination in thoracic DRGs (note labeled sensory fibers), spinal cord (note labeled neurons inviscera-related Rexed laminaX), DMV, sensory medullary lateral reticular nucleus (LRN), and parasubthalamicnucleus of the hypothalamus (PSTn).

(F) In VGx mice, HSV-LSL-TK-Tomato injected into the stomach of Nos1^Cre mice labeled DMV, LRN, and PSTn. The stomach-recipient LRN field partially overlapped with the forelimb-recipient LRN field defined by forelimb injections of HSV-EGFP. Data are represented as mean ± SEM in all figures. Scale bars, 100 μM.

See also Figure S5 and Table S1.