@article{1c14abd0e02c4e9ea4f444d3be8689c8,
title = "Diametric neural ensemble dynamics in parkinsonian and dyskinetic states",
abstract = "Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson's disease with the dopamine precursor l-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during l-DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, l-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in l-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.",
author = "Parker, {Jones Griffith} and Marshall, {Jesse D.} and Biafra Ahanonu and Wu, {Yu Wei} and Kim, {Tony Hyun} and Grewe, {Benjamin F.} and Yanping Zhang and Li, {Jin Zhong} and Ding, {Jun B.} and Ehlers, {Michael D.} and Schnitzer, {Mark J.}",
note = "Funding Information: We appreciate support from HHMI, the Stanford CNC Program, Stanford Photonics Research Center, Pfizer and a GG Technologies gift fund; fellowships from Stanford (J.D.M., T.H.K.), the Helen Hay Whitney Foundation (J.D.M.), the US National Institutes of Health (J.G.P., J.B.D.), HHMI (B.A.), the US National Science Foundation (B.A.), the Bill and Melinda Gates Foundation (B.A.), and the Swiss National Science Foundation (B.F.G.). We thank L. Burns, L. Kitch, E. Hamel, J. Lecoq, M. Larkin, T. Fieblinger, S. Ganguli, A. Girasole, A. Graybiel, A. Kreitzer, R. Malenka and A. Nelson for technical assistance and discussion, Inscopix Inc. for technical support and upgrades, and B. Rossi for scientific illustration Funding Information: Acknowledgements We appreciate support from HHMI, the Stanford CNC Program, Stanford Photonics Research Center, Pfizer and a GG Technologies gift fund; fellowships from Stanford (J.D.M., T.H.K.), the Helen Hay Whitney Foundation (J.D.M.), the US National Institutes of Health (J.G.P., J.B.D.), HHMI (B.A.), the US National Science Foundation (B.A.), the Bill & Melinda Gates Foundation (B.A.), and the Swiss National Science Foundation (B.F.G.). We thank L. Burns, L. Kitch, E. Hamel, J. Lecoq, M. Larkin, T. Fieblinger, S. Ganguli, A. Girasole, A. Graybiel, A. Kreitzer, R. Malenka and A. Nelson for technical assistance and discussion, Inscopix Inc. for technical support and upgrades, and B. Rossi for scientific illustration. Publisher Copyright: {\textcopyright} 2018 Macmillan Publishers Ltd., part of Springer Nature.",
year = "2018",
month = may,
day = "10",
doi = "10.1038/s41586-018-0090-6",
language = "English (US)",
volume = "557",
pages = "177--182",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7704",
}