1996 Fiscal Year Final Research Report Summary
Roles and mechanisms of glutamate receptors in integrative brain function
| Project/Area Number |
07407005
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKANISHI Shigetada Kyoto University, Medicine, Professor, 医学研究科, 教授 (20089105)
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| Project Period (FY) |
1995 – 1996
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| Keywords | NMDA receptor / metabotropic glutamate receptor / knockout mouse / memory and learning / visual processing / hippocampus / cerebellum / Ca^<2+> oscillation |
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| Research Abstract |
The aim of this research is to explore fundamental mechanisms underlying brain function by investigating the function and role of diverse members of glutamate receptors. We have succeeded in generating various knockout mice lacking different glutamate receptor subunits or subtypes by gene targeting and have elucidated the following novel mechanisms :
1.mGluR6 is responsible for synaptic transmission from photoreceptors to ON bipolar cells in the visual system and contributes to discrimination of visual contrasts.
2.mGluR2 is responsible for induction of long-term depression at the hippocampal mossy fiber-CA3 synapses, and contrary to current theory of hippocampal function, this deppression is not involved in spatial learning.
3.NMDA receptor NR2A and NR2C subunits in cerebellar granule cells are essential for motor coordination.
4.mGluR5 and mGluR1, though both coupling to the IP_3/Ca^<2+> signaling, elicit oscillatory and non-oscillatory responses of intracellular Ca^<2+> mobilization, respectively, and the oscillatory Ca^<2+> response of mGluR5 results from protein kinase C phosphorylation of a specific threonine of mGluR5.
5.The structure-activity relationships of agonists and antagonists of the different mGluR subtypes have been elucidated by synthesizing and analyzing a large number of phenylglycine derivatives and other compounds.
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