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

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.

Pubmed ID: 20498043

Authors

  • An MC
  • Lin W
  • Yang J
  • Dominguez B
  • Padgett D
  • Sugiura Y
  • Aryal P
  • Gould TW
  • Oppenheim RW
  • Hester ME
  • Kaspar BK
  • Ko CP
  • Lee KF

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

June 8, 2010

Associated Grants

  • Agency: NICHD NIH HHS, Id: HD034534
  • Agency: NINDS NIH HHS, Id: NS044420
  • Agency: NINDS NIH HHS, Id: NS047345
  • Agency: NINDS NIH HHS, Id: NS055028
  • Agency: NICHD NIH HHS, Id: R01 HD034534
  • Agency: NICHD NIH HHS, Id: R01 HD034534-13
  • Agency: NINDS NIH HHS, Id: R01 NS044420
  • Agency: NINDS NIH HHS, Id: R01 NS044420-05
  • Agency: NINDS NIH HHS, Id: R01 NS047345
  • Agency: NINDS NIH HHS, Id: R01 NS047345-04
  • Agency: NINDS NIH HHS, Id: R01 NS055028
  • Agency: NINDS NIH HHS, Id: R01 NS060833
  • Agency: NINDS NIH HHS, Id: R01 NS060833-03
  • Agency: NINDS NIH HHS, Id: R01 NS060833-04

Mesh Terms

  • Acetylation
  • Acetylcholine
  • Animals
  • Carbachol
  • Cell Differentiation
  • Cholinergic Agonists
  • Mice
  • Neuromuscular Junction
  • Receptors, Nicotinic