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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<jats:sub>2<\/jats:sub>mAChRs were present solely in motor neurons, whereas M<jats:sub>1<\/jats:sub>, M<jats:sub>3<\/jats:sub>, and M<jats:sub>5<\/jats:sub>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<jats:sub>2\/4<\/jats:sub>-preferring antagonist, induced terminal sprouting and terminal withdrawal, but no muscle fiber atrophy. Consistent with this observation, M<jats:sub arrange=\"stagger\">2<\/jats:sub><jats:sup arrange=\"stagger\">\u2212\/\u2212<\/jats:sup>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<jats:sub arrange=\"stagger\">2<\/jats:sub><jats:sup arrange=\"stagger\">\u2212\/\u2212<\/jats:sup>NMJs without sprouting. Moreover, compensatory sprouting after paralysis or partial denervation was normal in mice deficient in M<jats:sub>2<\/jats:sub>or other mAChR subtypes. We also found that many NMJs of M<jats:sub arrange=\"stagger\">5<\/jats:sub><jats:sup arrange=\"stagger\">\u2212\/\u2212<\/jats:sup>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<jats:sub>2<\/jats:sub>and that muscle fiber growth is defective without M<jats:sub>5<\/jats:sub>. Subtype-specific muscarinic signaling provides a novel means for coordinating activity-dependent development and maintenance of the tripartite synapse.<\/jats:p>","DOI":"10.1523\/jneurosci.2276-09.2009","type":"journal-article","created":{"date-parts":[[2009,11,25]],"date-time":"2009-11-25T23:18:28Z","timestamp":1259191108000},"page":"14942-14955","source":"Crossref","is-referenced-by-count":60,"title":["Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses"],"prefix":"10.1523","volume":"29","author":[{"given":"Megan C.","family":"Wright","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilatha","family":"Potluri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Dentcheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Gautam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Tessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Wess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Rich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Jin","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2009,11,25]]},"reference":[{"key":"2023041303412711000_29.47.14942.1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706780"},{"key":"2023041303412711000_29.47.14942.2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(88)90217-1"},{"key":"2023041303412711000_29.47.14942.3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707746"},{"key":"2023041303412711000_29.47.14942.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00475-2"},{"key":"2023041303412711000_29.47.14942.5","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374835"},{"key":"2023041303412711000_29.47.14942.6","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1523\/JNEUROSCI.10-03-00894.1990","article-title":"In vivo visualization of the growth of pre- and postsynaptic elements of neuromuscular junctions in the mouse","volume":"10","author":"Balice-Gordon","year":"1990","journal-title":"J Neurosci"},{"key":"2023041303412711000_29.47.14942.7","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1523\/JNEUROSCI.10-08-02660.1990","article-title":"Neuromuscular junctions shrink and expand as muscle fiber size is manipulated: in vivo observations in the androgen-sensitive bulbocavernosus muscle of mice","volume":"10","author":"Balice-Gordon","year":"1990","journal-title":"J Neurosci"},{"key":"2023041303412711000_29.47.14942.8","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1113\/jphysiol.1978.sp012307","article-title":"Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles","volume":"278","author":"Brown","year":"1978","journal-title":"J Physiol"},{"key":"2023041303412711000_29.47.14942.9","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21143"},{"key":"2023041303412711000_29.47.14942.10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0031-6997(24)01362-0","article-title":"International Union of Pharmacology. 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