Back to Search
Start Over
Sympathetic Input to Multiple Cell Types in Mouse and Human Colon Produces Region-Specific Responses.
- Source :
-
Gastroenterology [Gastroenterology] 2021 Mar; Vol. 160 (4), pp. 1208-1223.e4. Date of Electronic Publication: 2020 Sep 24. - Publication Year :
- 2021
-
Abstract
- Background & Aims: The colon is innervated by intrinsic and extrinsic neurons that coordinate functions necessary for digestive health. Sympathetic input suppresses colon motility by acting on intrinsic myenteric neurons, but the extent of sympathetic-induced changes on large-scale network activity in myenteric circuits has not been determined. Compounding the complexity of sympathetic function, there is evidence that sympathetic transmitters can regulate activity in non-neuronal cells (such as enteric glia and innate immune cells).<br />Methods: We performed anatomical tracing, immunohistochemistry, optogenetic (GCaMP calcium imaging, channelrhodopsin), and colon motility studies in mice and single-cell RNA sequencing in human colon to investigate how sympathetic postganglionic neurons modulate colon function.<br />Results: Individual neurons in each sympathetic prevertebral ganglion innervated the proximal or distal colon, with processes closely opposed to multiple cell types. Calcium imaging in semi-intact mouse colon preparations revealed changes in spontaneous and evoked neural activity, as well as activation of non-neuronal cells, induced by sympathetic nerve stimulation. The overall pattern of response to sympathetic stimulation was unique to the proximal or distal colon. Region-specific changes in cellular activity correlated with motility patterns produced by electrical and optogenetic stimulation of sympathetic pathways. Pharmacology experiments (mouse) and RNA sequencing (human) indicated that appropriate receptors were expressed on different cell types to account for the responses to sympathetic stimulation. Regional differences in expression of α-1 adrenoceptors in human colon emphasize the translational relevance of our mouse findings.<br />Conclusions: Sympathetic neurons differentially regulate activity of neurons and non-neuronal cells in proximal and distal colon to promote distinct changes in motility patterns, likely reflecting the distinct roles played by these 2 regions.<br /> (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Colon cytology
Colon drug effects
Colon physiology
Female
Ganglia, Sympathetic drug effects
Gastrointestinal Motility drug effects
Guanethidine pharmacology
Humans
Intestinal Mucosa cytology
Intestinal Mucosa drug effects
Intestinal Mucosa innervation
Intestinal Mucosa physiology
Male
Mice
Models, Animal
Myenteric Plexus cytology
Myenteric Plexus drug effects
Neurons drug effects
Neurons physiology
Optogenetics
Prazosin pharmacology
RNA-Seq
Single-Cell Analysis
Yohimbine pharmacology
Colon innervation
Ganglia, Sympathetic physiology
Gastrointestinal Motility physiology
Myenteric Plexus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 160
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 32980343
- Full Text :
- https://doi.org/10.1053/j.gastro.2020.09.030