A Novel Mode of Sympathetic Reflex Activation Mediated by the Enteric Nervous System

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Enteric viscerofugal neurons provide a pathway by which the enteric nervous system (ENS), otherwise confined to the gut wall, can activate sympathetic neurons in prevertebral ganglia. Firing transmitted through these pathways is currently considered fundamentally mechanosensory. The mouse colon generates a cyclical pattern of neurogenic contractile activity, called the colonic motor complex (CMC). Motor complexes involve a highly coordinated firing pattern in myenteric neurons with a frequency of ∼2 Hz. However, it remains unknown how viscerofugal neurons are activated and communicate with the sympathetic nervous system during this naturally-occurring motor pattern. Here, viscerofugal neurons were recorded extracellularly from rectal nerve trunks in isolated tube and flat-sheet preparations of mouse colon held at fixed circumferential length. In freshly dissected preparations, motor complexes were associated with bursts of viscerofugal firing at 2 Hz that aligned with 2-Hz smooth muscle voltage oscillations. This behavior persisted during muscle paralysis with nicardipine. Identical recordings were made after a 4- to 5-d organotypic culture during which extrinsic nerves degenerated, confirming that recordings were from viscerofugal neurons. Single unit analysis revealed the burst firing pattern emerging from assemblies of viscerofugal neurons differed from individual neurons, which typically made partial contributions, highlighting the importance and extent of ENS-mediated synchronization. Finally, sympathetic neuron firing was recorded from the central nerve trunks emerging from the inferior mesenteric ganglion. Increased sympathetic neuron firing accompanied all motor complexes with a 2-Hz burst pattern similar to viscerofugal neurons. These data provide evidence for a novel mechanism of sympathetic reflex activation derived from synchronized firing output generated by the ENS.

Original languageEnglish
Article numberENEURO.0187-20.2020
Pages (from-to)1-18
Number of pages18
Issue number4
Publication statusPublished - Jul 2020

Bibliographical note

This is an open-access article distributed under the terms of the CreativeCommons Attribution 4.0 International license, which permits unrestricted use,distribution and reproduction in any medium provided that the original work is properly attributed.


  • enteric nervous system
  • intestinofugal
  • motor complex
  • prevertebral ganglia
  • sympathetic nervous system
  • viscerofugal


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