| First Author | Foong JP | Year | 2015 |
| Journal | J Neurosci | Volume | 35 |
| Issue | 18 | Pages | 7106-15 |
| PubMed ID | 25948261 | Mgi Jnum | J:221646 |
| Mgi Id | MGI:5641272 | Doi | 10.1523/JNEUROSCI.4175-14.2015 |
| Citation | Foong JP, et al. (2015) Changes in Nicotinic Neurotransmission during Enteric Nervous System Development. J Neurosci 35(18):7106-15 |
| abstractText | 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 alpha3, alpha4, alpha7, beta2, and beta4 nAChR subunits were already expressed at low levels in the E11.5 gut and by E14.5 and, thereafter, alpha3 and beta4 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 alpha3beta4 receptors reduced electrically and chemically evoked calcium responses at E12.5, E14.5, and P0. In addition to the alpha3beta4 antagonist, antagonists to alpha3beta2 and alpha4beta2 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 alpha7 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. |
