Abstract | BACKGROUND: The microbiome is essential for normal myenteric intrinsic primary afferent neuron (IPAN) excitability. These neurons control gut motility and modulate gut-brain signaling by exciting extrinsic afferent fibers innervating the enteric nervous system via an IPAN to extrinsic fiber sensory synapse. We investigated effects of germ-free (GF) status and conventionalization on extrinsic sensory fiber discharge in the mesenteric nerve bundle and IPAN electrophysiology, and compared these findings with those from specific pathogen-free (SPF) mice. As we have previously shown that the IPAN calcium-dependent slow afterhyperpolarization (sAHP) is enhanced in GF mice, we also examined the expression of the calcium-binding protein calbindin in these neurons in these different animal groups. METHODS: IPAN sAHP and mesenteric nerve multiunit discharge were recorded using ex vivo jejunal gut segments from SPF, GF, or conventionalized (CONV) mice. IPANs were excited by adding 5 μM TRAM-34 to the serosal superfusate. We probed for calbindin expression using immunohistochemical techniques. KEY RESULTS: SPF mice had a 21% increase in mesenteric nerve multiunit firing rate and CONV mice a 41% increase when IPANs were excited by TRAM-34. For GF mice, this increase was barely detectable (2%). TRAM-34 changed sAHP area under the curve by -77 for SPF, +3 for GF, or -54% for CONV animals. Calbindin-immunopositive neurons per myenteric ganglion were 36% in SPF, 24% in GF, and 52% in CONV animals. CONCLUSIONS & INFERENCES: The intact microbiome is essential for normal intrinsic and extrinsic nerve function and gut-brain signaling.
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Authors | K A McVey Neufeld, A Perez-Burgos, Y K Mao, J Bienenstock, W A Kunze |
Journal | Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
(Neurogastroenterol Motil)
Vol. 27
Issue 5
Pg. 627-36
(May 2015)
ISSN: 1365-2982 [Electronic] England |
PMID | 25727007
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 John Wiley & Sons Ltd. |
Chemical References |
- Calbindins
- Pyrazoles
- TRAM 34
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Topics |
- Action Potentials
(drug effects, physiology)
- Animals
- Calbindins
(metabolism)
- Enteric Nervous System
(drug effects, metabolism, physiology)
- Female
- Gastrointestinal Microbiome
(physiology)
- Germ-Free Life
- Jejunum
(innervation, metabolism, microbiology)
- Mice
- Myenteric Plexus
(drug effects, metabolism, physiology)
- Neurons, Afferent
(drug effects, physiology)
- Pyrazoles
(pharmacology)
- Specific Pathogen-Free Organisms
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