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

    Research output: Contribution to journalArticleAcademicpeer-review

    6 Citations (Scopus)

    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
    Original languageUndefined
    Pages (from-to)1486-1494
    Number of pages9
    JournalMovement disorders
    Volume29
    Issue number12
    DOIs
    Publication statusPublished - 2014

    Keywords

    • EWI-24973
    • BSS-Electrical Neurostimulation
    • oscillations
    • globus pallidus
    • METIS-305980
    • IR-91590
    • Connexin-36
    • Confocal Microscopy

    Cite this

    @article{7b7f901f285a410fa1dc6fc4369dddea,
    title = "Pallidal gap junctions - Triggers of synchrony in Parkinson's disease?",
    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. {\circledC} 2014 International Parkinson and Movement Disorder Society",
    keywords = "EWI-24973, BSS-Electrical Neurostimulation, oscillations, globus pallidus, METIS-305980, IR-91590, Connexin-36, Confocal Microscopy",
    author = "B.C. Schwab and Tjitske Heida and Yan Zhao and {van Gils}, {Stephanus A.} and {van Wezel}, {Richard Jack Anton}",
    note = "eemcs-eprint-24973",
    year = "2014",
    doi = "10.1002/mds.25987",
    language = "Undefined",
    volume = "29",
    pages = "1486--1494",
    journal = "Movement disorders",
    issn = "0885-3185",
    publisher = "Wiley",
    number = "12",

    }

    Pallidal gap junctions - Triggers of synchrony in Parkinson's disease? / Schwab, B.C.; Heida, Tjitske; Zhao, Yan; van Gils, Stephanus A.; van Wezel, Richard Jack Anton.

    In: Movement disorders, Vol. 29, No. 12, 2014, p. 1486-1494.

    Research output: Contribution to journalArticleAcademicpeer-review

    TY - JOUR

    T1 - Pallidal gap junctions - Triggers of synchrony in Parkinson's disease?

    AU - Schwab, B.C.

    AU - Heida, Tjitske

    AU - Zhao, Yan

    AU - van Gils, Stephanus A.

    AU - van Wezel, Richard Jack Anton

    N1 - eemcs-eprint-24973

    PY - 2014

    Y1 - 2014

    N2 - 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

    AB - 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

    KW - EWI-24973

    KW - BSS-Electrical Neurostimulation

    KW - oscillations

    KW - globus pallidus

    KW - METIS-305980

    KW - IR-91590

    KW - Connexin-36

    KW - Confocal Microscopy

    U2 - 10.1002/mds.25987

    DO - 10.1002/mds.25987

    M3 - Article

    VL - 29

    SP - 1486

    EP - 1494

    JO - Movement disorders

    JF - Movement disorders

    SN - 0885-3185

    IS - 12

    ER -