Vagal sensory neurons profusely innervate the mouse gall bladder

The biliary system consisting of bile ducts and the gall bladder plays a crucial role in digestion and its function is controlled by both humoral and neural mechanisms. Despite the intense pain associated with gall bladder and bile duct pathologies, little is known about the sensory innervation, particularly sensory innervation by the vagus nerve. Here using anterograde viral tracing from either the left or right nodose ganglion, we demonstrate the presence of a dense sensory innervation of the murine gall bladder by vagal afferents. Entering via the cystic duct, bundles of vagal sensory axons travel along blood vessels from the neck towards the fundus of the gall bladder, where individual axons divide copiously to innervate large territories of the gall bladder wall. Reminiscent of the stomach wall, some vagal afferent axons end in intramuscular array-like endings or in laminar endings within gall bladder ganglia or in the tunica fibromuscularis. However, most axons form a variety of non-distinct endings mostly in the muscle layer. The innervation pattern is consistent with the detection of both mechanical and chemical stimuli. This calls for functional studies determining specific sensory modalities, and translational studies exploring their possible involvement in immune regulation, pain sensation, and interoceptive capacity.