Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia

Tim Fieblinger, Steven M. Graves, Luke E. Sebel, Cristina Alcacer, Joshua L. Plotkin, Tracy S. Gertler, C. Savio Chan, Myriam Heiman, Paul Greengard, M. Angela Cenci, D. James Surmeier

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149 Scopus citations

Abstract

The striatum is widely viewed as the fulcrum of pathophysiology in Parkinsonâ €™ s disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses.

Original languageEnglish (US)
Article number5316
JournalNature communications
Volume5
DOIs
StatePublished - 2014
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by USPHSG NS34696, NS041234, NS084735 and the JPB Foundation to D.J.S. and P.G., the IDP foundation to D.J.S. and by grants to M.A.C. from the European Community‘s Seventh Framework Programme FP7, the Basal Ganglia Disorders Linnaeus Consortium (BAGADILICO), the Swedish Research Council, the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), and the Olle Engkvist Foundation.

Publisher Copyright:
©2014 Macmillan Publishers Limited. All rights reserved.

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