• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Synaptic regulation in the cerebellum and motor control

開催日 2014/9/11
時間 9:00 - 11:00
会場 Room E(301)
Chairperson(s) 平井 宏和 / Hirokazu Hirai (群馬大学大学院医学系研究科神経生理学分野 / Department of Neurophysiology, Gunma University Graduate School of Medicine, Japan)
平野 丈夫 / Tomoo Hirano (京都大学理学研究科 生物物理 / Department of Biophysics, Graduate School of Science, Kyoto University, Japan)

Impairment of synaptic transmission that induces cerebellar ataxia and the underlying molecular mechanisms

  • S1-E-1-4
  • 平井 宏和 / Hirokazu Hirai:1 
  • 1:群馬大院医神経生理 / Department of Neurophysiology, Gunma University Graduate School of Medicine, Japan 

The cerebellum plays crucial roles in controlling sensorimotor functions. The neural output from the cerebellar cortex is transmitted solely by Purkinje cells (PCs), whose impairment causes cerebellar ataxia. Parallel fiber (PF) to PC synaptic transmission is mediated by postsynaptic ionotropic glutamate receptors and the metabotropic glutamate receptor subtype 1 (mGluR1). Previous studies including knockout of the mGluR1 or blockade of mGluR1 function by the specific antibody showed that mGluR signaling is crucial for cerebellar function and that defect of mGluR signaling results in severe ataxia. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disorder caused by the expansion of a polyglutamine tract in the ataxin-1 protein. The onset is approximately 4th decade of the life and the patients show progressive cerebellar ataxia. To date, no fundamental treatments for SCA1 have been elucidated. We found that SCA1 model mice show selective impairment of mGluR signaling in PCs without affecting the fast synaptic transmission. The mGluR signaling in SCA1 model mice was almost comparable with wild-type littermates at 3 weeks of age, but progressively impaired thereafter, which started in parallel with the onset of behavioral defects at 5 weeks of age, suggesting that the early behavioral impairment in SCA1 is caused by impediment of mGluR signaling in PCs. In this presentation, I summarize the relevance of mGluR defects to patients manifesting cerebellar ataxia.

Copyright © Neuroscience2014. All Right Reserved.