The gut-brain axis rewired: adding a functional vagal nicotinic “sensory synapse”
Abstract
It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse."
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The vagus nerve is activated in response to specific bacteria.
“Previous studies have shown that the vagus nerve is activated in response to specific bacteria (Perez-Burgos et al., 2014; Perez-Burgos et al., 2012)”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as Perez-Burgos et al., 2014
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- Authors
- Perez‐Burgos, A., Mao, Y., Bienenstock, J., & Kunze, W. A.
- Affiliations
- McMaster Brain‐Body Institute St. Joseph's Healthcare Hamilton Ontario Canada
- St. Joseph’s Healthcare Hamilton (CA)
- Corresponding author
- Kunze, Wolfgang A.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2014-04-09
- Volume
- 28
- Issue
- 7
- Pages
- 3064-3074
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1986501752
- Cited by
- 91
- References
- 69
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 9 · 2023: 3 · 2022: 12 · 2021: 9 · 2020: 11 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 10 · 2015: 6
- FWCI
- 8.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consejo Nacional de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gut-brain axis, vagal afferents, intrinsic primary afferent neurons, nicotinic acetylcholine receptors, synaptic transmission, mesenteric nerves, myenteric plexus, calcium channel blockade, gut microbiota, visceral hypersensitivity
- MeSH terms
- Action Potentials, Animals, Brain, Jejunum, Male, Neurons, Afferent, Receptors, Nicotinic, Synapses, Vagus Nerve, Mice, Lacticaseibacillus rhamnosus
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