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The gut microbiome restores intrinsic and extrinsic nerve function in germ‐free mice accompanied by changes in calbindin
Author(s) -
McVey Neufeld K. A.,
PerezBurgos A.,
Mao Y. K.,
Bienenstock J.,
Kunze W. A.
Publication year - 2015
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12534
Subject(s) - calbindin , myenteric plexus , neuroscience , biology , sensory system , enteric nervous system , electrophysiology , calcium binding protein , colocalization , medicine , endocrinology , microbiology and biotechnology , immunohistochemistry , immunology , calcium
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. IPAN s 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 IPAN s 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.