Enteric Control of the Sympathetic Nervous System

The autonomic nervous system that regulates the gut is divided into sympathetic (SNS), parasympathetic (PNS), and enteric nervous systems (ENS). They inhibit, permit, and coordinate gastrointestinal motility, respectively. A fourth pathway, “extrinsic sensory neurons,” connect gut to the central nervous system, mediating sensation. The ENS resides within the gut wall and its activities are critical for life; ENS failure to populate the gut in development is lethal without intervention. “Viscerofugal neurons” are a distinctive class of enteric neurons, being the only type that escapes the gut wall. They form a unique circuit: their axons project out of the gut wall and activate sympathetic neurons, which then project back to the gut, and inhibit gut movements. For 80 years viscerofugal/sympathetic circuits were thought to have a restricted role, mediating simple sensory-motor reflexes. New data shows viscerofugal and sympathetic neurons behaving unexpectedly, compelling a re-evaluation of these circuits: both viscerofugal and sympathetic neurons transmit higher order, synchronized firing patterns that originate within the ENS. This identifies them as driving long-range motility control between different gut regions. There is need for gut motor control over distances beyond the range of ENS circuits, yet no mechanism has been identified to date. The entero-sympathetic circuits are ideally suited to meet this need. Here we provide an overview of the structure and functions of these peripheral sympathetic circuits, including new data showing the firing patterns generated by enteric networks can transmit through sympathetic neurons.