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Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses
Journal article   Open access   Peer reviewed

Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses

Megan C. Wright, Srilatha Potluri, Xueyong Wang, Eva Dentcheva, Dinesh Gautam, Alan Tessler, Juergen Wess, Mark M. Rich, Young-Jin Son and Deborah J Clegg
The Journal of neuroscience, v 29(47), pp 14942-14955
25 Nov 2009
DOI: https://doi.org/10.1523/JNEUROSCI.2276-09.2009
PMID: 19940190
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
http://www.jneurosci.org/content/29/47/14942.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1523/JNEUROSCI.2276-09.2009View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
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 sprouting. Moreover, compensatory sprouting after paralysis or partial denervation was normal in mice deficient in M-2 or other mAChR subtypes. We also found that many NMJs of M-5(-/-) mice were exceptionally small and reduced in proportion to the size of parental muscle fibers. These findings show that axon terminals are unstable without M-2 and that muscle fiber growth is defective without M-5. Subtype-specific muscarinic signaling provides a novel means for coordinating activity-dependent development and maintenance of the tripartite synapse.

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55 citations in Web of Science
50 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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