Distinct muscarinic acetylcholine receptor subtypes contribute to stability and growth, but not compensatory plasticity, of neuromuscular synapses.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Megan C WrightYoung-Jin Son

Abstract

Muscarinic acetylcholine receptors (mAChRs) modulate synaptic function, but whether they influence synaptic structure remains unknown. At neuromuscular junctions (NMJs), mAChRs have been implicated in compensatory sprouting of axon terminals in paralyzed or denervated muscles. Here we used pharmacological and genetic inhibition and localization studies of mAChR subtypes at mouse NMJs to demonstrate their roles in synaptic stability and growth but not in compensatory sprouting. M(2) mAChRs were present solely in motor neurons, whereas M(1), M(3), and M(5) mAChRs were associated with Schwann cells and/or muscle fibers. Blockade of all five mAChR subtypes with atropine evoked pronounced effects, including terminal sprouting, terminal withdrawal, and muscle fiber atrophy. In contrast, methoctramine, an M(2/4)-preferring antagonist, induced terminal sprouting and terminal withdrawal, but no muscle fiber atrophy. Consistent with this observation, M(2)(-/-) but no other mAChR mutant mice exhibited spontaneous sprouting accompanied by extensive loss of parental terminal arbors. Terminal sprouting, however, seemed not to be the causative defect because partial loss of terminal branches was common even in the M(2)(-/-) NMJs without sprou...Continue Reading

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Citations

May 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Mahru C AnKuo-Fen Lee
Oct 28, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Haipeng ZhuChristopher M Gomez
Mar 25, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alessandro Di MaioYoung-Jin Son
Dec 11, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ke LiAngelo C Lepore
Sep 17, 2016·The Journal of Physiology·Danielle ArbourRichard Robitaille
Jan 11, 2017·Muscle & Nerve·Maria R JonesMichael L Garcia
Jul 19, 2018·Assay and Drug Development Technologies·Hermann A M Mucke
Feb 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Víctor Cilleros-MañéMaria Angel Lanuza
Apr 7, 2020·Journal of the Peripheral Nervous System : JPNS·Madeleine E CunninghamHugh J Willison
Dec 2, 2017·Annual Review of Physiology·Lei LiLin Mei
Dec 19, 2020·Biological Reviews of the Cambridge Philosophical Society·Diego ZeladaJuan P Henríquez
Jun 17, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·V Cilleros-MañéM A Lanuza
Apr 6, 2021·Aging and Disease·Sandra Fuertes-Alvarez, Ander Izeta

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