Do gap junctions regulate synchrony in the parkinsonian basal ganglia?

B.C. Schwab

    Research output: ThesisPhD Thesis - Research UT, graduation UT

    120 Downloads (Pure)

    Abstract

    Patients with Parkinson’s disease (PD) typically suffer severely from different types of symptoms. Motor symptoms, restricting the patients’ ability to perform controlled movements in daily life, are of special clinical interest and have been related to neural activity in the basal ganglia. Low-frequency oscillations, bursting (short periods of high-frequency spiking) and especially synchrony of basal ganglia activity emerge after dopamine depletion that follows cell death in the substantia nigra pars compacta. These changes are all believed to contribute to motor symptoms. In this thesis, we described a possible mechanism for the emergence of synchrony in the basal ganglia of PD patients based on gap junctions in the external part of the globus pallidus (GPe), using a combination of experimental and computational methods. We first describe why we focus on the GPe (Chapter 2), and then seek experimental evidence for the occurrence of gap junctions in GPe (Chapter 3). A computational model of the basal ganglia is used in Chapter 4 to estimate the effect of sparse gap junction coupling between GPe neurons on basal ganglia activity. Finally, in Chapter 5, we study the impact of basal ganglia activity in general on downstream structures. In conclusion, this work introduces a novel theory: contributions of gap junctions to synchrony and potentially motor symptoms of PD patients. It remains to be shown how many of the detected gap junctions are functional and how large their impact on beta oscillations as well as motor symptoms is.
    Original languageUndefined
    Awarding Institution
    • University of Twente
    Supervisors/Advisors
    • van Gils, Stephanus A., Supervisor
    • van Wezel, Richard Jack Anton, Supervisor
    Thesis sponsors
    Award date22 Apr 2016
    Place of PublicationEnschede
    Publisher
    Print ISBNs978-90-365-4070-4
    DOIs
    Publication statusPublished - 22 Apr 2016

    Keywords

    • Neuroscience
    • oscillations
    • biophysics
    • EWI-26982
    • Gap junctions
    • IR-100288
    • METIS-316464
    • Computational modeling

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