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Document Type
Article
Publication Date
1-2018
DOI
https://doi.org/10.1016/j.celrep.2017.12.095
Abstract
Dopamine (DA) loss in Parkinson’s disease (PD) alters the function of striatal projection neurons (SPNs) and causes motor deficits, but DA replacement can induce further abnormalities. A key pathological change in animal models and patients is SPN hyperactivity; however, the role of glutamate in altered DA responses remains elusive. We tested the effect of locally applied AMPAR or NMDAR antagonists on glutamatergic signaling in SPNs of parkinsonian primates. Following a reduction in basal hyperactivity by antagonists at either receptor, DA inputs induced SPN firing changes that were stable during the entire motor response, in clear contrast with the typically unstable effects. The SPN activity reduction over an extended putamenal area controlled the release of involuntary movements in the “on” state and therefore improved motor responses to DA replacement. These results demonstrate the pathophysiological role of upregulated SPN activity and support strategies to reduce striatal glutamate signaling for PD therapy.
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This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Scimemi, Annalisa; Singh, Arun; Jenkins, Meagan A.; Burke, Kenneth J. Jr.; Beck, Goichi; Jenkins, Andrew; Jenkins, Andrew; Traynelis, Stephen F.; and Papa, Stella M., "Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates" (2018). Biological Sciences Faculty Scholarship. 38.
https://scholarsarchive.library.albany.edu/biology_fac_scholar/38
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This article is made available under the Scholars Archive Terms of Use.
Comments
This is the Publisher’s PDF of the following article made available by Cell Reports: https://doi.org/10.1016/j.celrep.2017.12.095