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Our studies revealed that the intrinsic excitability and functional corticostriatal connectivity of SPNs in dyskinetic mice oscillate between LID on- and off-states in a cell- and state-specific manner. Although triggered by levodopa, these oscillations in SPN properties depended on both dopaminergic and cholinergic signaling. Disrupting M1 muscarinic receptor signaling specifically in indirect pathway SPNs or deleting its downstream signaling partner CalDAG-GEFI blunted the levodopa-induced alterations in functional connectivity, enhanced the motoric benefits of levodopa, and attenuated LID severity.<\/jats:p>","DOI":"10.1126\/sciadv.adv8224","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:59:02Z","timestamp":1764788342000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":10,"title":["State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson\u2019s disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7097-9387","authenticated-orcid":true,"given":"Shenyu","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."},{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815 USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-4208","authenticated-orcid":true,"given":"Qiaoling","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."},{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815 USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5497-6944","authenticated-orcid":true,"given":"David","family":"Wokosin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-277X","authenticated-orcid":true,"given":"Linqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6626-7435","authenticated-orcid":true,"given":"Tatiana","family":"Tkatch","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA."},{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815 USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill R.","family":"Crittenden","sequence":"additional","affiliation":[{"name":"McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4326-7720","authenticated-orcid":true,"given":"Ann M.","family":"Graybiel","sequence":"additional","affiliation":[{"name":"McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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