{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:46:54Z","timestamp":1790948814741,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["154\/14"],"award-info":[{"award-number":["154\/14"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["155\/14"],"award-info":[{"award-number":["155\/14"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1959\/22"],"award-info":[{"award-number":["1959\/22"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["646886"],"award-info":[{"award-number":["646886"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Levodopa treatment, the gold standard therapy for Parkinson's disease, can lead to levodopa\u2010induced dyskinesias (LIDs). Recent studies in acute brain slices have implicated the neural dynamics of striatal cholinergic interneurons (CINs) in the pathophysiology of LID, reporting that their discharge becomes more bursty in dyskinetic mice. However, little is known about how parkinsonism and levodopa affect CINs in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used microendoscopic imaging in the dorsal striatum of the genetically encoded Ca\n                      <jats:sup>2+<\/jats:sup>\n                      indicator, GCaMP6f, expressed in cholinergic neurons. We imaged the collective, simultaneous activity of several molecularly identified CINs in the dorsal striatum, in control mice, as well as in mice rendered parkinsonian with 6\u2010hydroxydopamine (6\u2010OHDA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that 6\u2010OHDA drove a levodopa\u2010insensitive increase in the baseline rate of activity of CINs and a reduction in their responsiveness to self\u2010initiated movement. Furthermore, levodopa treatment (even before the appearance of LIDs) drove an increase in the amplitude of the individual Ca\n                      <jats:sup>2+<\/jats:sup>\n                      events (perhaps indicative of more burst\u2010like discharge), which correlated with a further reduction in the number of CINs responsive to movement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      6\u2010OHDA treatment disrupts the robust encoding of movement by CINs. Levodopa disrupts the activity of CINs, possibly making them more bursty in vivo, even before the manifestation of LIDs. Thus, molecularly\u2010identified CINs are implicated in the pathophysiology of parkinsonism. Not only does levodopa fail to restore their normal dynamics, but it actually exacerbates their abnormal burstiness. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70018","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T08:48:46Z","timestamp":1757926126000},"page":"2457-2468","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Levodopa Disrupts Activity Patterns and Encoding of Movement in Striatal Cholinergic Interneurons of Behaving Mice"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-7960","authenticated-orcid":false,"given":"Yara","family":"Atamna","sequence":"first","affiliation":[{"name":"Department of Medical Neurobiology, Institute of Medical Research Israel \u2013 Canada, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5634-4484","authenticated-orcid":false,"given":"Lior","family":"Tiroshi","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute of Medical Research Israel \u2013 Canada, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2704-0873","authenticated-orcid":false,"given":"Nadine","family":"Wattad","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute of Medical Research Israel \u2013 Canada, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0638-532X","authenticated-orcid":false,"given":"Naomi","family":"Gilin","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute of Medical Research Israel \u2013 Canada, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4506-7754","authenticated-orcid":false,"given":"Shelly","family":"Gilad","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute of Medical Research Israel \u2013 Canada, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-4708","authenticated-orcid":false,"given":"Noa","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute of Medical Research Israel \u2013 Canada, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5740-4087","authenticated-orcid":false,"given":"Joshua A.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, Institute of Medical Research Israel \u2013 Canada, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.059"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(10)83011-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0090-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","unstructured":"ZhaiS CuiQ WokosinD et al.State\u2010dependent modulation of spiny projection neurons controls levodopa\u2010induced dyskinesia in a mouse model of Parkinson's 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