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The basal ganglia in Parkinson's disease: Current concepts and unexplained observations

Authors

  • Jose A. Obeso PhD, MD,

    Corresponding author
    1. Departments of Neurology, Neurophysiology and Neurosurgery, Clinica Universitaria and Medical School, Neuroscience Centre, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
    • Clinica Universitaria, Avenida Pio XII, 36, Pamplona, 31008, Spain
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  • Concepcio Marin PhD, MD,

    1. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
    2. Laboratori de Neurologia Experimental, Fundació Clínic-Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain
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  • C. Rodriguez-Oroz PhD, MD,

    1. Departments of Neurology, Neurophysiology and Neurosurgery, Clinica Universitaria and Medical School, Neuroscience Centre, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Javier Blesa,

    1. Departments of Neurology, Neurophysiology and Neurosurgery, Clinica Universitaria and Medical School, Neuroscience Centre, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • B. Benitez-Temiño PhD,

    1. Departments of Neurology, Neurophysiology and Neurosurgery, Clinica Universitaria and Medical School, Neuroscience Centre, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
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  • Juan Mena-Segovia PhD, MD,

    1. Medical Research Centre Anatomical Neuropharmacology Unit, University of Oxford, Oxford, United Kingdom
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  • Manuel Rodríguez PhD, MD,

    1. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
    2. Department of Physiology, Medical School, Universidad de La Laguna, Tenerife, Spain
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  • C. Warren Olanow MD, FRCPC

    1. Department of Neurology, Mount Sinai School of Medicine, New York, NY
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  • Potential conflict of interest: This article is part of a supplement sponsored by Boehringer Ingelheim (BI). J.A.O. has served once in the past three years as a consultant in an advisory board meeting of BI and GlaxoSmithKline, and on a single occasion for Novartis Pharmaceutica. C.M., C.R.-O., J.B., B.B.-T., J.M.-S., and M.R. declare that they have no financial relationship with BI. J.M.-S. was funded by the Medical Research Council UK and the Parkinson's Disease Society of the UK. M. R. has no financial or consulting relationships with pharmaceutical enterprises. C.W. O. has served as a consultant to BI, Novartis, Teva, Merck Serono, and Ceregene.

Abstract

The pathophysiology of Parkinson's disease is reviewed in light of recent advances in the understanding of the functional organization of the basal ganglia (BG). Current emphasis is placed on the parallel interactions between corticostriatal and corticosubthalamic afferents on the one hand, and internal feedback circuits modulating BG output through the globus pallidus pars interna and substantia nigra pars reticulata on the other. In the normal BG network, the globus pallidus pars externa emerges as a main regulatory station of output activity. In the parkinsonian state, dopamine depletion shifts the BG toward inhibiting cortically generated movements by increasing the gain in the globus pallidus pars externa-subthalamic nucleus-globus pallidus pars interna network and reducing activity in “direct” cortico-putaminal-globus pallidus pars interna projections. Standard pharmacological treatments do not mimic the normal physiology of the dopaminergic system and, therefore, fail to restore a functional balance between corticostriatal afferents in the so-called direct and indirect pathways, leading to the development of motor complications. This review emphasizes the concept that the BG can no longer be understood as a “go-through” station in the control of movement, behavior, and emotions. The growing understanding of the complexity of the normal BG and the changes induced by DA depletion should guide the development of more efficacious therapies for Parkinson's disease. Ann Neurol 2008;64 (suppl):S30–S46

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