Selective activation of DMN cholinergic neurons reduces circulating and pancreatic markers of acute pancreatitis Acute pancreatitis was induced in ChAT-ChR2-YFP mice by two intraperitoneal injections of caerulein (50 µg/kg). A fiberoptic cannula was placed in the left DMN and mice were then subjected to blue light stimulation (473 nm, 20 Hz, 25% duty cycle, 8-12 mW, 5 minutes), yellow light stimulation (593.5 nm, 20 Hz, 25% duty cycle, 8-12 mW, 5 minutes), or no laser stimulation. Mice were euthanized 4 hours after the final dose of caerulein. (A) Compared to non-caerulein-injected controls, caerulein-injected mice show significantly increased serum amylase levels consistent with the induction of acute pancreatitis. Optogenetic stimulation with blue light, but not with yellow light, significantly decreases serum amylase levels. Data are represented as individual mouse data points with mean ± SEM. One-way ANOVA: no caerulein vs yellow laser vs no laser (****P ≤ 0.0001, n = 7-11). (B) Optogenetic stimulation with blue light decreases pancreatic levels of (D) IL-6, (E) CXCL-1, and (F) MCP-1, but not (C) IL-1β. Data are represented as individual mouse data points with mean ± SEM. One-way ANOVA, (**P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001, n = 9-11). ns, not significant.