{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:09:10Z","timestamp":1790327350925,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS59910"],"award-info":[{"award-number":["NS59910"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dyskinesias are a disabling motor complication that arises with prolonged <jats:sc>l<\/jats:sc>\u2010dopa treatment. Studies using D1 receptor drugs and genetically modified mice suggest that medium spiny neurons expressing D1 receptors play a primary role in <jats:sc>l<\/jats:sc>\u2010dopa\u2013induced dyskinesias. However, the specific role of these neurons in dyskinesias is not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used optogenetics, which allows for precise modulation of select neurons in vivo, to investigate whether striatal D1\u2010expressing medium spiny neuron activity regulates abnormal involuntary movements or dyskinesia in parkinsonian mice. D1\u2010cre mice unilaterally lesioned with 6\u2010hydroxydopamine received striatal injections of cre\u2010dependent channelrhodopsin2 virus or control virus. After stable virus expression, the effect of optical stimulation on dyskinesia was tested in <jats:sc>l<\/jats:sc>\u2010dopa\u2013na\u00efve and <jats:sc>l<\/jats:sc>\u2010dopa\u2013primed mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Single\u2010pulse and burst\u2010optical stimulation of D1\u2010expressing medium spiny neurons induced dyskinesias in <jats:sc>l<\/jats:sc>\u2010dopa\u2013na\u00efve channelrhodopsin2 mice. In stably dyskinetic mice, <jats:sc>l<\/jats:sc>\u2010dopa injection induced dyskinesia to a similar or somewhat greater extent than optical stimulation. Combined <jats:sc>l<\/jats:sc>\u2010dopa administration and stimulation resulted in an additive increase in dyskinesias, indicating that other mechanisms also contribute. Molecular studies indicate that changes in extracellular signal\u2010regulated kinase phosphorylation in D1\u2010expressing medium spiny neurons are involved. Optical stimulation did not ameliorate parkinsonism in <jats:sc>l<\/jats:sc>\u2010dopa\u2013na\u00efve mice. However, it improved parkinsonism in <jats:sc>l<\/jats:sc>\u2010dopa\u2013primed mice to a similar extent as <jats:sc>l<\/jats:sc>\u2010dopa administration. None of the stimulation paradigms enhanced dyskinesia or modified parkinsonism in <jats:sc>l<\/jats:sc>\u2010dopa\u2013na\u00efve or <jats:sc>l<\/jats:sc>\u2010dopa\u2013primed control virus mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The data provide direct evidence that striatal D1\u2010expressing medium spiny neuron stimulation is sufficient to induce dyskinesias and contributes to the regulation of motor control. \u00a9 2017 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26955","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T04:03:51Z","timestamp":1488513831000},"page":"538-548","source":"Crossref","is-referenced-by-count":59,"title":["Striatal D1 medium spiny neuron activation induces dyskinesias in parkinsonian mice"],"prefix":"10.1002","volume":"32","author":[{"given":"Xiomara A.","family":"Perez","sequence":"first","affiliation":[{"name":"Bioscience 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