Aberrant striatal plasticity is specifically associated with dyskinesia following levodopa treatment

Authors

  • Pauline Belujon PhD,

    Corresponding author
    1. Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, PA, USA
    • Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260 USA
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    • The first two authors have contributed equally.

  • Daniel J. Lodge PhD,

    1. Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, PA, USA
    Current affiliation:
    1. Department of Pharmacology, UTHSCSA, San Antonio, Texas, USA
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    • The first two authors have contributed equally.

  • Anthony A. Grace PhD

    1. Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, PA, USA
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  • Potential conflicts of interest: Nothing to report.

Abstract

Chronic levodopa treatment for Parkinson's disease often results in the development of abnormal involuntary movement, known as L-dopa-induced dyskinesia (LIDs). Studies suggest that LIDs may be associated with aberrant corticostriatal plasticity. Using in vivo extracellular recordings from identified Type I and Type II medium spiny striatal neurons, chronic L-dopa treatment was found to produce abnormal corticostriatal information processing. Specifically, after chronic L-dopa treatment in dopamine-depleted rats, there was a transition from a cortically evoked long-term depression (LTD) to a complementary but opposing form of plasticity, long-term potentiation, in Type II “indirect” pathway neurons. In contrast, LTD could still be induced in Type I neurons. Interestingly, the one parameter that correlated best with dyskinesias was the inability to de-depress established LTD in Type I medium spiny striatal neurons. Taken as a whole, we propose that the induction of LIDs is due, at least in part, to an aberrant induction of plasticity within the Type II indirect pathway neurons combined with an inability to de-depress established plastic responses in Type I neurons. Such information is critical for understanding the cellular mechanisms underlying one of the major caveats to L-dopa therapy. © 2010 Movement Disorder Society

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