Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility

Abstract

The gastrointestinal tract is the only internal organ to have evolved with its own independent nervous system, known as the enteric nervous system (ENS). This Review provides an update on advances that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central nervous system have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut–brain axis. The enteric nervous system (ENS) is essential for life and controls the function of the gastrointestinal tract. Here, an overview of sensory transduction and neural circuits in the ENS is provided, yielding insights into the generation of gastrointestinal motility. In vertebrates, the enteric nervous system (ENS) is critical for gastrointestinal function. There has been much progress in understanding the mechanisms by which mechanical or chemical stimulation of the gut is converted into neural activity within the ENS and propulsive motility. Mechanosensory elements critical for distension-evoked colonic peristalsis have been identified to lie in the myenteric plexus and/or circular muscle of the gastrointestinal tract and do not require the mucosa or submucosal plexus. Evidence suggests that substances released from cells in the mucosa (such as enteroendocrine cells) can modulate ENS activity, but the release of mediators like serotonin is not required for distension-evoked peristalsis or for colonic migrating motor complexes. Fundamental differences have been revealed in the mechanisms of activation of extrinsic spinal afferent nerves compared with those of intrinsic sensory nerves in the same region of the bowel. Recent refinements in optogenetic technologies now permit the stimulation of specific neurochemical classes of neurons in the ENS to elucidate function.