title: Changes in Nicotinic Neurotransmission during Enteric Nervous System Development.
abstract: Acetylcholine-activating pentameric nicotinic receptors (nAChRs) are an essential mode of neurotransmission in the enteric nervous system (ENS). In this study, we examined the functional development of specific nAChR subtypes in myenteric neurons using Wnt1-Cre;R26R-GCaMP3 mice, where all enteric neurons and glia express the genetically encoded calcium indicator, GCaMP3. Transcripts encoding α3, α4, α7, β2, and β4 nAChR subunits were already expressed at low levels in the E11.5 gut and by E14.5 and, thereafter, α3 and β4 transcripts were the most abundant. The effect of specific nAChR subtype antagonists on evoked calcium activity in enteric neurons was investigated at different ages. Blockade of the α3β4 receptors reduced electrically and chemically evoked calcium responses at E12.5, E14.5, and P0. In addition to the α3β4 antagonist, antagonists to α3β2 and α4β2 also significantly reduced responses by P10-11 and in adult preparations. Therefore, there is an increase in the diversity of functional nAChRs during postnatal development. However, an α7 nAChR antagonist had no effect at any age. Furthermore, at E12.5 we found evidence for unconventional receptors that were responsive to the nAChR agonists 1-dimethyl-4-phenylpiperazinium and nicotine, but were insensitive to the general nicotinic blocker, hexamethonium. Migration, differentiation, and neuritogenesis assays did not reveal a role for nAChRs in these processes during embryonic development. In conclusion, there are significant changes in the contribution of different nAChR subunits to synaptic transmission during ENS development, even after birth. This is the first study to investigate the development of cholinergic transmission in the ENS.
authors.affiliation: Departments of Physiology and.
authors.forename: Jaime Pei Pei
authors.initials: JP
authors.lastname: Foong
authors.affiliation: Anatomy and Neuroscience, University of Melbourne, Victoria 3010, Australia and.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Hirst
authors.affiliation: Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, 3000 Leuven, Belgium.
authors.forename: Marlene M
authors.initials: MM
authors.lastname: Hao
authors.affiliation: Anatomy and Neuroscience, University of Melbourne, Victoria 3010, Australia and.
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: McKeown
authors.affiliation: Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, 3000 Leuven, Belgium.
authors.forename: Werend
authors.initials: W
authors.lastname: Boesmans
authors.affiliation: Anatomy and Neuroscience, University of Melbourne, Victoria 3010, Australia and.
authors.forename: Heather M
authors.identifier: http://orcid.org/0000-0002-0457-8710
authors.initials: HM
authors.lastname: Young
authors.affiliation: Departments of Physiology and.
authors.forename: Joel C
authors.identifier: http://orcid.org/0000-0002-7518-7717
authors.initials: JC
authors.lastname: Bornstein
authors.affiliation: Laboratory for Enteric NeuroScience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, 3000 Leuven, Belgium Pieter.VandenBerghe@med.kuleuven.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vanden Berghe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017615:Enteric Nervous System / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011247:Pregnancy; D011978:Receptors, Nicotinic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic
keywords: development; enteric nervous system; neurotransmission; nicotinic receptor