Abdominal vagotomy reveals majority of small intestinal mucosal afferents labeled in nav1.8cre‐rosa26tdTomato mice are vagal in origin

• Published in: Journal of comparative neurology (1911) 2020-04, Vol.528 (5), p.816-839
• Main Authors: Serlin, Hannah K., Fox, Edward A.
• Format: Article
• Language: English
• Subjects: Dorsal root ganglia; Duodenum; Innervation; Intestine; Mesentery; Morphology; Mucosa; mucosal innervation; Rodents; RRID:AB_10013483; RRID:AB_2338000; RRID:IMSR_JAX:007905; RRID:SCR_002865; RRID:SCR_014199; RRID:SCR_014300; Sensory neurons; Sodium channels (voltage-gated); Surgery; vagotomy; Vagus nerve; Villus
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24791

Vagal afferents innervating the small intestinal mucosa regulate feeding, gastrointestinal (GI) digestive, and immune functions. Their anatomical‐functional characterization has been impeded by the inability to selectively label and manipulate them. Nav1.8‐Cre‐tdTomato mice label 80% of nodose and dorsal root ganglia neurons. Here, the origin of these neuron's terminals and their distribution in the small intestinal mucosa were examined by quantitatively comparing tdTomato‐labeled innervation in nonoperated (control), subdiaphragmatic vagotomy (VAGX), and sham‐operated mice. Control mice exhibited a large proximal‐to‐distal decrease and a moderate mesentery‐to‐antimesentery decrease in villus innervation. VAGX reduced this innervation to a greater degree proximally (91–93%) than distally (65–72%), resulting in flat proximal‐distal distributions. Therefore, estimates of vagal villus afferent distributions (control minus VAGX) paralleled control distributions, but were slightly reduced in magnitude. Compared with villus afferents, crypt innervation exhibited a muted proximal‐to‐distal decrease in control mice and a smaller loss after VAGX (45–48%). Sham‐operated mice exhibited similar distributions of villus and crypt afferents as control mice, suggesting surgery did not contribute to the effects of VAGX. Most crypt and villus afferent terminals along the entire proximal‐distal small intestinal axis had similar morphology to those previously reported in the proximal duodenum, but the density of terminal branches varied. Our findings suggest the majority of small intestinal mucosal innervation labeled in Nav1.8‐Cre‐tdTomato mice is vagal in origin. Therefore, these mice will be valuable for studying vagal mucosal afferent morphology, interactions with other GI elements, plasticity, and function. This study evaluated the usefulness of the nav1.8cre‐rosa26tdTomato mouse model in selectively labeling vagal mucosal afferents in the small intestine. Quantitative comparison of tdTomato‐labeled innervation along the length of the small intestinal mucosa in Nav1.8‐Cre‐tdTomato control, bilateral subdiaphragmatic vagotomy (VAGX), and sham VAGX mice revealed that the nav1.8cre‐rosa26tdTomato mouse model preferentially labels a large proportion of the vagal afferents innervating the small intestinal mucosa. Mapping the distribution of tdTomato‐labeled innervation in control mice revealed that vagal afferents exhibit proximal‐to‐distal and mesenteric‐to‐anti‐mesenteric g