| Project/Area Number |
12307005
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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 Shigatada Graduate School of Biostudies, Professor, 生命科学研究科, 教授 (20089105)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Satoshi Graduate School of Medicine KYOTO UNIVERSITY, Research Associates, 医学研究科, 助手 (70303815)
WATANABE Dai Graduate School of Medicine KYOTO UNIVERSITY, Research Associates, 医学研究科, 助手 (90303817)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥42,490,000 (Direct Cost: ¥37,300,000、Indirect Cost: ¥5,190,000)
Fiscal Year 2001: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
Fiscal Year 2000: ¥20,000,000 (Direct Cost: ¥20,000,000)
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| Keywords | selective neuronal cell ablation / network / Parkinson's disease / abuse of drugs / directional selectivity of vision / glutamate receptor / adaptor protein / 3-D structure of receptor / 基底核神経回路 / 運動制御 / 網膜神経回路 |
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| Research Abstract |
This project was directed toward investigation of the function and regulation of a neural network and regulatory mechanisms of glutamate receptor function. The main results of this investigation are as follows:
(1) The basal ganglia network is a key element whose abnormality is implicated in Parkinson's disease and abuse of drugs. Striatal cholinergic ihterneurons were specifically ablated from the adult basal ganglia network, using immunotoxin-mediated cell targeting techniques. This study revealed that the acerylcholine-dopamine interaction is concertedly and adaptively regulated in basal ganglia network and plays an essential role in controlling motor balance. Furthermore, elimination of cholinergic interneurons in the adult nucleus accumbens disclosed a marked enhancement in sensitivity to cocaine in both acute and long-lasting actions associated with cocaine addiction.
(2) We demonstrated that ablation of retinal starburst amacrine cells abolished not only directional selectivity of ganglion cell responses but also an optokinetic eye reflex derived by stimulus movement, indicating that synaptic integration via starburst cells plays a pivotal role in information processing that stabilizes image motion.
(3) We identified a novel PDZ protein termed tamalin and indicated that tamalin links a protein complex formation of group 1 metabotropic glutamate receptors (mGluRs) and guanine nucleotide exchange factors and contributes to intracellular targeting of mGluRs.
(4) Our study indicated that NMDA receptors and BDNF selectively upregulate mRNA encoding a adaptor hormer la protein in cultured cerebellar granule cells via the MAP kinase cascade.
(5) We succeeded in crystallization of the glutamate-binding domain of mGluR1 and unraveled the structural basis for glutamate recognition of mGluR.
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