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Neural mechanism of voluntary movement and development of therapeutic approach

開催日 2014/9/11
時間 14:00 - 16:00
会場 Room B(501)
Chairperson(s) 山下 俊英 / Toshihide Yamashita (大阪大学大学院 医学系研究科 分子神経科学 / Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Japan)
星 英司 / Eiji Hoshi (東京都医学総合研究所 前頭葉機能プロジェクト / Frontal Lobe Function Project, Tokyo Metropolitan Institute of Medical Science, Japan)

Physiological Basis for Movement Disorders and Their Therapeutics through the Basal Ganglia Circuitry

  • S1-B-2-5
  • 南部 篤 / Atsushi Nambu:1 
  • 1:生理学研究所・生体システム / Div of System Neurophysiol, Natl Inst for Physiol Sci, Okazaki, Japan 

Information from the motor cortices is processed in the basal ganglia (BG) and returns to the original motor cortices via the thalamus. In the BG circuitry, the striatum and the subthalamic nucleus (STN) are the input structures of the BG, while the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr) are the output nuclei. The input and output stations are connected by three pathways, i.e., cortico-striato-GPi/SNr direct, cortico-striato-external pallido (GPe)-STN-GPi/SNr indirect, and cortico-STN-GPi/SNr hyperdirect pathways. Signals through the hyperdirect, direct and indirect pathways sequentially reach the output nuclei, GPi/SNr, and modulate their activity dynamically. Thus, only a selected motor program is released at a selected timing, while other competing motor programs are suppressed, through the succeeding GPi-thalamo-cortical pathway.
The activity imbalance among the hyperdirect, direct and indirect pathways causes hypokinetic and hyperkinetic movement disorders. In Parkinson's disease (PD), signals through the hyperdirect and indirect pathways are enhanced, and those through the direct pathway are reduced in both spatial and temporal domains. Thus, intended motor programs cannot be released, resulting in akinesia. On the other hand, in dystonia, signals through the direct pathway are enhanced spatiotemporally. Thus, unintended movements are randomly released, resulting in involuntary movements. These dynamic activity changes in the BG can explain the neural mechanisms underlying hypokinetic and hyperkinetic movement disorders.
Inactivation of the STN, which interrupts both the hyperdirect and indirect pathways, ameliorates PD symptoms. Applying high frequency stimulation, known as deep brain stimulation (DBS), to the STN or GPi also ameliorates motor symptoms. GPi-DBS completely inhibits spontaneous firings of GPi neurons and blocks all responses mediated by the hyperdirect, direct and indirect pathways. These findings suggest that dissociating inputs and outputs to and from the stimulation site to disrupt the abnormal information flow is the common mechanism for the effectiveness of stereotactic surgery.

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