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

Nature Reviews Gastroenterology & Hepatology volume 17, pages 338–351 (2020)Cite this article

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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.

Key points

  • 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.

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Fig. 1: Key developments in the enteric nervous system.
Fig. 2: The major extrinsic neural pathways between the ENS and spinal cord and brain.
Fig. 3: Different types of intrinsic sensory neurons and extrinsic sensory nerve endings in the enteric nervous system.
Fig. 4: Possible mechanisms underlying the activation of two major classes of intrinsic sensory neuron in the ENS.
Fig. 5: Major intrinsic neuronal circuits in the large intestine active during neurogenic motor patterns.

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Acknowledgements

H.H. was supported by grants from the NIH, R01GM101218, R01DK103901 and R01AA027065, Washington University School of Medicine Digestive Disease Research Core Center (NIDDK P30 DK052574), The Center for the Study of Itch of the Department of Anaesthesiology at Washington University School of Medicine. N.J.S. is supported by NH&MRC of Australia, grants APP1156427 and APP1156416.

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  1. College of Medicine and Public Health & Centre for Neuroscience, Flinders University, Adelaide, Australia

    Nick J. Spencer

  2. Department of Anesthesiology, The Center for the Study of Itch, Washington University School of Medicine, St Louis, MO, USA

    Hongzhen Hu

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Spencer, N.J., Hu, H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat Rev Gastroenterol Hepatol 17, 338–351 (2020). https://doi.org/10.1038/s41575-020-0271-2

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