TY - JOUR
T1 - The gut-brain axis
T2 - spatial relationship between spinal afferent nerves and 5-HT-containing enterochromaffin cells in mucosa of mouse colon
AU - Dodds, Kelsi N.
AU - Travis, Lee
AU - Kyloh, Melinda A.
AU - Jones, Lauren A.
AU - Keating, Damien J.
AU - Spencer, Nick J.
PY - 2022/5
Y1 - 2022/5
N2 - Cross talk between the gastrointestinal tract and brain is of significant relevance for human health and disease. However, our understanding of how the gut and brain communicate has been limited by a lack of techniques to identify the precise spatial relationship between extrinsic nerve endings and their proximity to specific cell types that line the inner surface of the gastrointestinal tract. We used an in vivo anterograde tracing technique, previously developed in our laboratory, to selectively label single spinal afferent axons and their nerve endings in mouse colonic mucosa. The closest three-dimensional distances between spinal afferent nerve endings and axonal varicosities to enterochromaffin (EC) cells, which contain serotonin (5-hydroxytryptamine; 5-HT), were then measured. The mean distances (± standard deviation) between any varicosity along a spinal afferent axon or its nerve ending, and the nearest EC cell, were 5.7 ± 6.0 μm (median: 3.6 μm) and 26.9 ± 18.6 μm (median: 24.1 μm), respectively. Randomization of the spatial location of EC cells revealed similar results to this actual data. These distances are ∼200-1,000 times greater than those between pre- and postsynaptic membranes (15-25 nm) that underlie synaptic transmission in the vertebrate nervous system. Our findings suggest that colonic 5-HT-containing EC cells release substances to activate centrally projecting spinal afferent nerves likely via diffusion, as such signaling is unlikely to occur with the spatial fidelity of a synapse.
AB - Cross talk between the gastrointestinal tract and brain is of significant relevance for human health and disease. However, our understanding of how the gut and brain communicate has been limited by a lack of techniques to identify the precise spatial relationship between extrinsic nerve endings and their proximity to specific cell types that line the inner surface of the gastrointestinal tract. We used an in vivo anterograde tracing technique, previously developed in our laboratory, to selectively label single spinal afferent axons and their nerve endings in mouse colonic mucosa. The closest three-dimensional distances between spinal afferent nerve endings and axonal varicosities to enterochromaffin (EC) cells, which contain serotonin (5-hydroxytryptamine; 5-HT), were then measured. The mean distances (± standard deviation) between any varicosity along a spinal afferent axon or its nerve ending, and the nearest EC cell, were 5.7 ± 6.0 μm (median: 3.6 μm) and 26.9 ± 18.6 μm (median: 24.1 μm), respectively. Randomization of the spatial location of EC cells revealed similar results to this actual data. These distances are ∼200-1,000 times greater than those between pre- and postsynaptic membranes (15-25 nm) that underlie synaptic transmission in the vertebrate nervous system. Our findings suggest that colonic 5-HT-containing EC cells release substances to activate centrally projecting spinal afferent nerves likely via diffusion, as such signaling is unlikely to occur with the spatial fidelity of a synapse.
KW - anterograde tracing
KW - enterochromaffin cell
KW - gut-brain axis
KW - serotonin
KW - spinal afferent
UR - http://www.scopus.com/inward/record.url?scp=85128488581&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1156427
UR - http://purl.org/au-research/grants/ARC/DP190103628
U2 - 10.1152/ajpgi.00019.2022
DO - 10.1152/ajpgi.00019.2022
M3 - Article
C2 - 35293258
AN - SCOPUS:85128488581
SN - 0193-1857
VL - 322
SP - G523-G533
JO - American Journal of Physiology-Gastrointestinal and Liver Physiology
JF - American Journal of Physiology-Gastrointestinal and Liver Physiology
IS - 5
ER -