{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:46:19Z","timestamp":1791895579498,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["HRZZ\u2010UIP\u20102019\u201004\u20108277"],"award-info":[{"award-number":["HRZZ\u2010UIP\u20102019\u201004\u20108277"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["DOK\u20102021\u201002\u20106169"],"award-info":[{"award-number":["DOK\u20102021\u201002\u20106169"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","award":["4013"],"award-info":[{"award-number":["4013"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Cholinergic premotor inputs to motoneurons support high levels of motor output when required. However, the possible role of these inputs in pathologically elevated muscle tone has not been characterised. To address this, we examined the modulatory effect of spinal acetylcholine (ACh) on experimental spastic paralysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Rats were injected with tetanus neurotoxin (TeNT, 33\u2013100\u2009pg, im) into gastrocnemius to induce sustained rigid hind\u2010paw extension and resistance to passive ankle flexion. The effects of spinal ACh on experimental hypertonia were probed by lumbar intrathecal application of the AChE inhibitor neostigmine (NEO) or a muscarinic M\n                      <jats:sub>2<\/jats:sub>\n                      receptor antagonist (AQ\u2010RA 741). Effects of NEO on extracellular ACh were measured in the facial nucleus after TeNT (33\u2009pg) or botulinum toxin A (BoNT\/A, 2\u00a0U) injection into the rat whisker pad. The intensity of TeNT\u2010evoked hindlimb hypertonia (10\u00a0pg, im) was assessed in mice with genetic ablation of cholinergic C bouton source interneurons (V0\n                      <jats:sub>C<\/jats:sub>\n                      interneurons).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      NEO augmented the severity of TeNT\u2010evoked hypertonia, whereas AQ\u2010RA 741 attenuated it. Local perfusion of NEO caused a BoNT\/A\u2010sensitive increase in extracellular ACh concentration. The involvement of cholinergic C boutons was corroborated by reduced hypertonia following TeNT challenge (10\u00a0pg, im) in V0\n                      <jats:sub>C<\/jats:sub>\n                      \u2010ablated mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      Our results suggest that spinal cholinergic transmission, associated with vesicular ACh release and M\n                      <jats:sub>2<\/jats:sub>\n                      signalling at C boutons, exacerbates experimental spastic paralysis. We reveal a new role for endogenous spinal ACh, with implications for developing new therapeutic approaches to treat spasticity and hyperkinetic movement disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70708","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:53:08Z","timestamp":1791892388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cholinergic inputs to motoneurons in the spinal cord augment focal muscle spasticity in rodents"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7016-1853","authenticated-orcid":false,"given":"Patrik","family":"Megli\u0107","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Neuropharmacology, Department of Pharmacology and Croatian Institute of Brain Research University of Zagreb School of Medicine  Zagreb 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