Analysis of molecular mechanisms for localization and functional modulation of metabotropic glutamate receptors in the central nervous system
| Project/Area Number |
14570106
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
NAKAJIMA Yoshiaki (2003) Kyoto University, Graduate School of Medicine, associate Professor, 医学研究科, 助教授 (10300724)
渡辺 大 (2002) 京都大学, 医学研究科, 助手 (90303817)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Dai Kyoto University, Graduate School of Medicine, assistant Professor, 医学研究科, 助手 (90303817)
中嶋 善明 京都大学, 医学研究科, 助教授 (10300724)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | glutamate receptor / cerebellum / reversible / Cajal-Retzius cells / striatum / acetylcholine / tamalin / scaffold protein / グルタミン酸 / シナプス |
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| Research Abstract |
In the cerebellar circuit, we studied the role and synaptic mechanisms of postsynaptic metabotropic glutamate receptor subtype 2 (mGluR2) at granule cell-Golgi cell synapses, using whole-cell recording of green fluorescent protein-positive Golgi cells of wild-type and mGluR2-deficient mice. We found that postsynaptic mGluR2 thus senses inputs from granule cells and is most likely important for spatiotemporal modulation of mossy fiber-granule cell transmission before distributing inputs to Purkinje cells.
The striatum in the basal ganglia-thalamocortical circuitry is a key neural substrate that is implicated in motor balance and procedural learning. The projection neurons in the striatum are dynamically modulated by nigrostriatal dopaminergic input and intrastriatal cholinergic input. The role of intrastriatal acetylcholine (ACh) in learning behaviors, however, remains to be fully clarified. In this investigation, we examine the involvement of intrastriatal ACh in different categories of
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learning by selectively ablating the striatal cholinergic neurons with use of immunotoxin-mediated cell targeting. We found that cholinergic modulation in the local striatal circuit plays a pivotal role in regulation of neural circuitry Involving reward-related procedural learning and working memory.
We developed a novel technique that allowed reversible suppression of glutamatergic neurotransmission in the cerebellar network. The transgenic mice will serve as an animal model to study the cerebellar function in motor coordination and learning.
Layer 1 In the developing cerebral cortex is populated by two basic neuronal cell types. Cajal-Retzius (CR) cells and non-CR cells. We generated transgenic mice in which green fluorescent protein (GFP) was driven by the promoter of metabotropic glutamate receptor subtype 2 and expressed specifically in CR cells during cortical development. The resuts imply that the layer 1 neurons dynamically change and play a distinct and integral role in the postnatal developing neocortex.
Tamalin is a scaffold protein that comprises multiple protein-interacting domains, including a 95-kDa postsynaptic density protein (PSD-95)/discs-large/ZQ-1 (PDZ) domain, a leucine-zipper region, and a carboxyl-terminal PDZ binding motif. Tamalin forms a complex with metabotropic glutamate receptors and guanine nucleotide exchange factor cytohesins and promotes intracellular trafficking and cell surface expression of group 1 metabotropic glutamate receptors. In the present study, using several different approaches we have shown that tamalin interacts with multiple neuronal proteins through Its distinct protein-binding domains. The results indicate that tamalin exists as a key element that forms a protein complex with multiple postsynaptic and protein-trafficking scaffold proteins. Less
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Report
(3 results)
Research Products
(17 results)
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[Publications] Hazama, M., Watanabe, D., Suzuki M., Mizoguchi, A., Pastan, I., Nakanishi, S.: "Different regulatory sequences are required for parvalbumin gene expression in skeletal muscles and neuronal cells of transgenic mice"Brain Res Mol Brain Res. 110. 53-66 (2002)
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[Publications] Kitano, J., Kimura.K., Yamazaki, Y., Soda, T., Shigemoto, R., Nakajima, Y., Nakanishi, S.: "Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins"J Neurosci. 22. 1280-1289 (2002)
