Functional identification of vagal afferent branch from the gastrointestinal organs by capsaicin administration in mice

The vagal nerves in mice run ventrally and dorsally below their diaphragm. They form four branches (common hepatic, R1; ventral gastric, R2; dorsal gastric, L1; celiac, L2) that project into the abdominal organs, such as the stomach, small intestine, and liver. To identify the vagal afferents that receive inputs from these organs, we examined the neural responses to the gastrointestinal and portal injection of capsaicin, a known stimulant of vagal afferents. The afferent fibers of the three branches (R1, R2, and L1) were activated following the intragastric (IG) injection of capsaicin in anesthetized mice. Moreover, the injection of a wheat germ agglutinin tracer into the stomach enabled the detection of positive cells in the nodose ganglion of intact mice, but not in vagotomized (VG) mice with transected R1, R2, and L1 branches. Capsaicin administered into the duodenum or portal vein activated the afferent neural activities of the R1 and L2 or R1, R2, and L1 branches, respectively. Moreover, IG injection of capsaicin increased the efferent sympathetic outflows to the brown adipose tissue and the kidney. The sympathetic response of the brown adipose tissue, but not the kidney, was abolished in the VG mice. In addition, an anorexigenic response to capsaicin was also abolished in the VG mice. Finally, increased vagal afferents were observed in diet-induced obese mice, which were comparable with the responses observed with capsaicin treatment of control mice. Thus, vagal afferents activated by capsaicin may contribute to the suppression of diet-induced obesity through efferent sympathoexcitation and appetite reduction.<b>NEW & NOTEWORTHY</b> In a mouse study, we identified input patterns from the gastrointestinal organs and liver to vagal afferents, with physiological evidence that there is no one-to-one correspondence between nerve branches and organs; multiple nerve branches receive inputs from a single organ. This new discovery is important as it contributes to elucidating the mechanisms of physiological function based on the vagal afferent pathway affected by nutrition, osmotic pressure, and hormones.