RT Journal Article
SR Electronic
T1 Changes in Nicotinic Neurotransmission during Enteric Nervous System Development
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7106
OP 7115
DO 10.1523/JNEUROSCI.4175-14.2015
VO 35
IS 18
A1 Jaime Pei Pei Foong
A1 Caroline S. Hirst
A1 Marlene M. Hao
A1 Sonja J. McKeown
A1 Werend Boesmans
A1 Heather M. Young
A1 Joel C. Bornstein
A1 Pieter Vanden Berghe
YR 2015
UL http://www.jneurosci.org/content/35/18/7106.abstract
AB 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.