New Insights on Extrinsic Innervation of the Enteric Nervous System and Non-neuronal Cell Types That Influence Colon Function

The enteric nervous system not only innervates the colon to execute various functions in a semi-autonomous manner but also receives neural input from three extrinsic sources, (1) vagal, (2) thoracolumbar (splanchnic), and (3) lumbosacral (pelvic) pathways, that permit bidirectional communication between the colon and central nervous system. Extrinsic pathways signal sensory input via afferent fibers, as well as motor autonomic output via parasympathetic or sympathetic efferent fibers, but the shared and unique roles for each pathway in executing sensory-motor control of colon function have not been well understood. Here, we describe the recently developed approaches that have provided new insights into the diverse mechanisms utilized by extrinsic pathways to influence colon functions related to visceral sensation, motility, and inflammation. Based on the cumulative results from anatomical, molecular, and functional studies, we propose pathway-specific functions for vagal, thoracolumbar, and lumbosacral innervation of the colon.