Identification of vagal afferent nerve endings in the mouse colon and their spatial relationship with enterochromaffin cells

Nick J. Spencer, Melinda A. Kyloh, Lee Travis, Timothy J. Hibberd

Research output: Contribution to journalArticlepeer-review

28 Downloads (Pure)

Abstract

Understanding how the gut communicates with the brain, via sensory nerves, is of significant interest to medical science. Enteroendocrine cells (EEC) that line the mucosa of the gastrointestinal tract release neurochemicals, including the largest quantity of 5-hydroxytryptamine (5-HT). How the release of substances, like 5-HT, from enterochromaffin (EC) cells activates vagal afferent nerve endings is unresolved. We performed anterograde labelling from nodose ganglia in vivo and identified vagal afferent axons and nerve endings in the mucosa of whole-mount full-length preparations of mouse colon. We then determined the spatial relationship between mucosal-projecting vagal afferent nerve endings and EC cells in situ using 3D imaging. The mean distances between vagal afferent nerve endings in the mucosa, or nearest varicosities along vagal afferent axon branches, and the nearest EC cell were 29.6 ± 19.2 μm (n = 107, N = 6) and 25.7 ± 15.2 μm (n = 119, N = 6), respectively. No vagal afferent endings made close contacts with EC cells. The distances between EC cells and vagal afferent endings are many hundreds of times greater than known distances between pre- and post-synaptic membranes (typically 10–20 nm) that underlie synaptic transmission in vertebrates. The absence of any close physical contacts between 5-HT-containing EC cells and vagal afferent nerve endings in the mucosa leads to the inescapable conclusion that the mechanism by which 5-HT release from ECs in the colonic mucosa occurs in a paracrine fashion, to activate vagal afferents.

Original languageEnglish
Pages (from-to)313-327
Number of pages15
JournalCell and Tissue Research
Volume396
Issue number3
Early online date22 Feb 2024
DOIs
Publication statusPublished - Jun 2024

Keywords

  • Enterochromaffin cell
  • Gut-brain axis
  • Serotonin
  • Spinal afferent
  • Vagal afferent anterograde tracing

Fingerprint

Dive into the research topics of 'Identification of vagal afferent nerve endings in the mouse colon and their spatial relationship with enterochromaffin cells'. Together they form a unique fingerprint.

Cite this