Innervation of the extrahepatic biliary tract

Abstract

The extrahepatic biliary tract is innervated by dense networks of extrinsic and intrinsic nerves that regulates smooth muscle tone and epithelial cell function of extrahepatic biliary tree. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical, and physiological characteristics that are distinct from the neurons of the enteric nervous system. Gallbladder neurons are relatively inexcitable, and their output is driven by vagal inputs and modulated by hormones, peptides released from sensory fibers, and inflammatory mediators. Gallbladder neurons are cholinergic and they can express a number of other neural active compounds, including substance P, galanin, nitric oxide, and vasoactive intestinal peptide. Sphincter of Oddi (SO) ganglia, which are connected to ganglia of the duodenum, appear to be comprised of distinct populations of excitatory and inhibitory neurons, based on their expression of choline acetyltransferase and substance P or nitric oxide synthase, respectively. While SO neurons likely receive vagal input and their activity is modulated by release of neuropeptides from sensory fibers, a significant source of excitatory synaptic input to these cells arise from the duodenum. This duodenum-SO circuit is likely to play an important role in the coordination of SO tone with gallbladder motility in the process of gallbladder emptying. Now that we have gained a relatively thorough understanding of the innervation of the biliary tree under healthy conditions, the way is paved for future studies of altered neural function in biliary disease.