@article {Won3090, author = {Lisa Won and Yunmin Ding and Pardeep Singh and Un Jung Kang}, title = {Striatal Cholinergic Cell Ablation Attenuates l-DOPA Induced Dyskinesia in Parkinsonian Mice}, volume = {34}, number = {8}, pages = {3090--3094}, year = {2014}, doi = {10.1523/JNEUROSCI.2888-13.2014}, publisher = {Society for Neuroscience}, abstract = {3,4-Dihydroxyphenyl-l-alanine (l-DOPA)-induced dyskinesia (LID) is a debilitating side effect of long-term dopamine replacement therapy in Parkinson{\textquoteright}s Disease. At present, there are few therapeutic options for treatment of LID and mechanisms contributing to the development and maintenance of these drug-induced motor complications are not well understood. We have previously shown that pharmacological reduction of cholinergic tone attenuates the expression of LID in parkinsonian mice with established dyskinesia after chronic l-DOPA treatment. The present study was undertaken to provide anatomically specific evidence for the role of striatal cholinergic interneurons by ablating them before initiation of l-DOPA treatment and determining whether it decreases LID. We used a novel approach to ablate striatal cholinergic interneurons (ChIs) via Cre-dependent viral expression of the diphtheria toxin A subunit (DT-A) in hemiparkinsonian transgenic mice expressing Cre recombinase under control of the choline acetyltransferase promoter. We show that Cre recombinase-mediated DT-A ablation selectively eliminated ChIs when injected into striatum. The depletion of ChIs markedly attenuated LID without compromising the therapeutic efficacy of l-DOPA. These results provide evidence that ChIs play a key and selective role in LID and that strategies to reduce striatal cholinergic tone may represent a promising approach to decreasing l-DOPA-induced motor complications in Parkinson{\textquoteright}s disease.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/34/8/3090}, eprint = {https://www.jneurosci.org/content/34/8/3090.full.pdf}, journal = {Journal of Neuroscience} }