{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:27:25Z","timestamp":1791840445998,"version":"4.3.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The pathophysiology of levodopa-induced dyskinesia (LID) in Parkinson\u2019s disease (PD) is not well understood. Experimental data from numerous investigations support the idea that aberrant activity of D<jats:sub>1<\/jats:sub> dopamine receptor-positive medium spiny neurons in the striatal direct pathway is associated with LID. However, a direct link between the real-time activity of these striatal neurons and dyskinetic symptoms remains to be established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined the effect of acute levodopa treatment on striatal c-Fos expression in LID using D<jats:sub>1<\/jats:sub>-Cre PD rats with dyskinetic symptoms induced by chronic levodopa administration. We studied the real-time dynamics of striatal D<jats:sub>1<\/jats:sub><jats:sup>+<\/jats:sup> neurons during dyskinetic behavior using GCaMP<jats:sub>6<\/jats:sub>-based <jats:italic>in vivo<\/jats:italic> fiber photometry. We also examined the effects of striatal D<jats:sub>1<\/jats:sub><jats:sup>+<\/jats:sup> neuronal deactivation on dyskinesia in LID rats using optogenetics and chemogenetic methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Striatal D<jats:sub>1<\/jats:sub><jats:sup>+<\/jats:sup> neurons in LID rats showed increased expression of c-Fos, a widely used marker for neuronal activation, following levodopa injection. Fiber photometry revealed synchronized overactivity of striatal D<jats:sub>1<\/jats:sub><jats:sup>+<\/jats:sup> neurons during dyskinetic behavior in LID rats following levodopa administration. Consistent with these observations, optogenetic deactivation of striatal D<jats:sub>1<\/jats:sub><jats:sup>+<\/jats:sup> neurons was sufficient to inhibit most of the dyskinetic behaviors of LID animals. Moreover, chemogenetic inhibition of striatal D<jats:sub>1<\/jats:sub><jats:sup>+<\/jats:sup> neurons delayed the onset of dyskinetic behavior after levodopa administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data demonstrated that aberrant activity of striatal D<jats:sub>1<\/jats:sub><jats:sup>+<\/jats:sup> neuronal population was causally linked with real-time dyskinetic symptoms in LID rats.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2022.783893","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:35:15Z","timestamp":1643866515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Striatal D1 Dopamine Neuronal Population Dynamics in a Rat Model of Levodopa-Induced Dyskinesia"],"prefix":"10.3389","volume":"14","author":[{"given":"Shasha","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqiong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongchi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/0166-2236(90)90107-l","article-title":"Functional architecture of basal ganglia circuits: neural substrates of parallel processing.","volume":"13","author":"Alexander","year":"1990","journal-title":"Trends Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/ana.20296","article-title":"Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia.","volume":"57","author":"Aubert","year":"2005","journal-title":"Ann. 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