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Publication : Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms.

First Author  An MC Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  23 Pages  10702-7
PubMed ID  20498043 Mgi Jnum  J:161300
Mgi Id  MGI:4457967 Doi  10.1073/pnas.1004956107
Citation  An MC, et al. (2010) Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proc Natl Acad Sci U S A 107(23):10702-7
abstractText  Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs increased motor axon branching and expanded innervation territory, suggesting that ACh negatively regulates synaptic growth through postsynaptic AChRs. However, in contrast to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs in agrin-deficient mice failed to restore deficits in pre- and postsynaptic differentiation, suggesting that ACh negatively regulates synaptic differentiation through nonpostsynaptic receptors. Consistent with this idea, the ACh agonist carbachol inhibited presynaptic specialization of motorneurons in vitro. Together, these data suggest that ACh negatively regulates axon growth and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms.
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