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The purpose of this study was to investigate whether Sol and<jats:styled-content style=\"fixed-case\">TA MN<\/jats:styled-content>s adapt to changes in cholinergic environment by differential regulation of their muscarinic receptors M2 (M2R). We examined<jats:italic>Chrm2<\/jats:italic>(M2R gene) transcript level, high\u2010affinity 3\u2010quinuclidinyl benzilate\u2010<jats:sup>3<\/jats:sup>H ([<jats:sup>3<\/jats:sup>H]<jats:styled-content style=\"fixed-case\">QNB<\/jats:styled-content>) ligand binding, distribution and density of M2R immunolabeling in lumbar (L) segments in intact and<jats:styled-content style=\"fixed-case\">SCT<\/jats:styled-content>rats, with or without inclusion of 5\u2010week treadmill locomotor training. We show that at the second week after<jats:styled-content style=\"fixed-case\">SCT<\/jats:styled-content>the levels of<jats:italic>Chrm2<\/jats:italic>transcript are reduced in the L3\u20136 segments, with [<jats:sup>3<\/jats:sup>H]<jats:styled-content style=\"fixed-case\">QNB<\/jats:styled-content>binding decreased selectively in the L5\u20136 segments, where ankle extensor<jats:styled-content style=\"fixed-case\">MN<\/jats:styled-content>s are predominantly located. At 5\u00a0weeks after<jats:styled-content style=\"fixed-case\">SCT<\/jats:styled-content>, [<jats:sup>3<\/jats:sup>H]<jats:styled-content style=\"fixed-case\">QNB<\/jats:styled-content>binding differences between the L3\u20134 and L5\u20136 segments are maintained, accompanied by higher density of M2R immunolabeling in the plasma membrane and cytoplasm of<jats:styled-content style=\"fixed-case\">TA<\/jats:styled-content>than Sol<jats:styled-content style=\"fixed-case\">MN<\/jats:styled-content>s and by enriched synaptic versus extrasynaptic M2R pools (52%<jats:styled-content style=\"fixed-case\">TA<\/jats:styled-content>vs. 25% Sol<jats:styled-content style=\"fixed-case\">MN<\/jats:styled-content>s). Training normalized M2R in<jats:styled-content style=\"fixed-case\">TA MN<\/jats:styled-content>s, improved locomotion, and reduced frequency of clonic episodes. Our findings indicate higher sensitivity of<jats:styled-content style=\"fixed-case\">TA<\/jats:styled-content>than Sol<jats:styled-content style=\"fixed-case\">MN<\/jats:styled-content>s to cholinergic signaling after<jats:styled-content style=\"fixed-case\">SCT<\/jats:styled-content>, which might shorten flexor twitches duration and contribute to generation of clonic movements. Synaptic enrichment in M2R density may reflect a compensatory mechanism activated in<jats:styled-content style=\"fixed-case\">TA<\/jats:styled-content>and Sol<jats:styled-content style=\"fixed-case\">MN<\/jats:styled-content>s to different extent in response to reduced strength of cholinergic signaling to each<jats:styled-content style=\"fixed-case\">MN<\/jats:styled-content>pool.<\/jats:p><jats:sec><jats:title>Open Practices<\/jats:title><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jnc14567-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p><jats:p>Open Science: This manuscript was awarded with the Open Materials Badge.<\/jats:p><jats:p>For more information see:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/cos.io\/our-services\/open-science-badges\/\">https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link><\/jats:p><\/jats:sec><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14567-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14567","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T16:36:58Z","timestamp":1534178218000},"page":"361-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Spinalization and locomotor training differentially affect muscarinic acetylcholine receptor type 2 abutting on \u03b1\u2010motoneurons innervating the ankle extensor and flexor muscles"],"prefix":"10.1111","volume":"147","author":[{"given":"Angelika","family":"Wi\u0119ckowska","sequence":"first","affiliation":[{"name":"Nencki Institute of Experimental Biology Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Gajewska\u2010Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Nencki Institute of Experimental Biology Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"G\u0142owacka","sequence":"additional","affiliation":[{"name":"Nencki Institute of Experimental Biology Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjun","family":"Ji","sequence":"additional","affiliation":[{"name":"Nencki Institute of Experimental Biology Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamil","family":"Grycz","sequence":"additional","affiliation":[{"name":"Nencki Institute of Experimental Biology 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