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In Parkinson's Disease (PD) patients, cortico\u2010striatal decoupling is widely reported while its onset and cellular mechanism remain largely unclear. Using dual\u2010site fiber photometry and Cre transgenic mouse lines, we examined activity coordination between the primary motor (M1) cortex and dorsal striatum (cortico\u2010striatal coupling) with cell\u2010type resolution. This method identifies motor behavior\u2010specific coupling patterns with different contributions from striatal D1R\u2010 and D2R\u2010expressing medium spiny neurons (MSNs). In an \u03b1\u2010synuclein preformed fibrils (PFF) induced PD\u2010like mouse model, cortico\u2010striatal coupling associated with digging behavior is selectively disrupted as early as two months post\u2010induction, whose progressive deterioration correlates with later\u2010onset behavioral deficits. Optogenetic disruption or enhancement\u00a0of cortico\u2010striatal coupling is sufficient to induce digging deficits in wild\u2010type mice or rescue such deficits in PFF\u2010injected mice, respectively. Furthermore, such decoupling is mainly mediated by impaired D1R MSNs, which can be rescued by D1 receptor activation or L\u2010DOPA. These findings demonstrate that early\u2010onset, behavior\u2010 and cell type\u2010specific cortico\u2010striatal decoupling emerges early during the development of PD\u2010like symptoms.<\/jats:p>","DOI":"10.1002\/advs.202513670","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T04:22:57Z","timestamp":1766550177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Behavior\u2010 and Cell Type\u2010Specific Cortico\u2010Striatal Decoupling in a Parkinson's Disease\u2010Like Mouse Model"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0205-1318","authenticated-orcid":false,"given":"Xu\u2010Ran","family":"Yao","sequence":"first","affiliation":[{"name":"Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of 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