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Dysregulation of striatal projection neurons in Parkinson’s disease

Journal of Neural Transmission volume 125, pages 449–460 (2018)Cite this article

Abstract

The loss of nigrostriatal dopamine (DA) is the primary cause of motor dysfunction in Parkinson’s disease (PD), but the underlying striatal mechanisms remain unclear. In spite of abundant literature portraying structural, biochemical and plasticity changes of striatal projection neurons (SPNs), in the past there has been a data vacuum from the natural human disease and its close model in non-human primates. Recently, single-cell recordings in advanced parkinsonian primates have generated new insights into the altered function of SPNs. Currently, there are also human data that provide direct evidence of profoundly dysregulated SPN activity in PD. Here, we review primate recordings that are impacting our understanding of the striatal dysfunction after DA loss, particularly through the analysis of physiologic correlates of parkinsonian motor behaviors. In contrast to recordings in rodents, data obtained in primates and patients demonstrate similar major abnormalities of the spontaneous SPN firing in the alert parkinsonian state. Furthermore, these studies also show altered SPN responses to DA replacement in the advanced parkinsonian state. Clearly, there is yet much to learn about the striatal discharges in PD, but studies using primate models are contributing unique information to advance our understanding of pathophysiologic mechanisms.

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Affiliations

  1. Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA, 30329, USA

    Goichi Beck, Arun Singh & Stella M. Papa

  2. Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30329, USA

    Stella M. Papa

Authors
  1. Goichi Beck
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  2. Arun Singh
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  3. Stella M. Papa
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Corresponding author

Correspondence to Stella M. Papa.

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Beck, G., Singh, A. & Papa, S.M. Dysregulation of striatal projection neurons in Parkinson’s disease. J Neural Transm 125, 449–460 (2018). https://doi.org/10.1007/s00702-017-1744-5

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  • DOI: https://doi.org/10.1007/s00702-017-1744-5

Keywords

  • Parkinson’s disease
  • Striatal projection neurons
  • Non-human primates
  • Direct and indirect pathways
  • Dyskinesia