• Open Access

Pallidal gap junctions-triggers of synchrony in Parkinson's disease?

Authors

  • Bettina C. Schwab,

    Corresponding author
    1. Applied Analysis, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands
    2. Biomedical Signals and Systems, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands
    • Correspondence to: Bettina C. Schwab, Applied Analysis, Department of Applied Mathematics, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands. Telephone: 0031640177295. E-Mail: b.c.schwab@utwente.nl

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  • Tjitske Heida,

    1. Biomedical Signals and Systems, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands
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  • Yan Zhao,

    1. Biomedical Signals and Systems, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands
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  • Stephan A. van Gils,

    1. Applied Analysis, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands
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  • Richard J. A. van Wezel

    1. Biomedical Signals and Systems, MIRA Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, The Netherlands
    2. Biophysics, Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands
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  • Funding agencies: We acknowledge funding of the Netherlands Organization for Scientific Research (NWO) on the NDNS+-project ”Desynchronization of Parkinsonian Oscillations in the Subthalamic Nucleus” and from MIRA, Institute for Biomedical Technology and Technical Medicine, University of Twente.

  • Relevant conflicts of interest/financial disclosures: B. C. Schwab receives funding of the Netherlands Organisation for Scientific Research (NWO) on the NDNS+-project ”Desynchronization of Parkinsonian Oscillations in the Subthalamic Nucleus” and from MIRA, Institute for Biomedical Technology and Technical Medicine, University of Twente. She receives human tissue from the Netherlands Brain Bank and is supported by the German National Academic Foundation.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. © 2014 International Parkinson and Movement Disorder Society

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