| Project/Area Number |
03102005
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKANISHI Shigetada Kyoto University Faculty of Medicine, Professor, 医学部, 教授 (20089105)
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| Co-Investigator(Kenkyū-buntansha) |
SHIGEMOTO Ryuichi Kyoto University faculty of Medicine Assistant Professor, 医学部, 助手 (20221294)
NAWA Hiroyuki Kyoto University Faculty of Medicine Associate Professor, 医学部, 助教授 (50183083)
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| Project Period (FY) |
1991 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥237,000,000 (Direct Cost: ¥237,000,000)
Fiscal Year 1994: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 1993: ¥50,000,000 (Direct Cost: ¥50,000,000)
Fiscal Year 1992: ¥52,000,000 (Direct Cost: ¥52,000,000)
Fiscal Year 1991: ¥85,000,000 (Direct Cost: ¥85,000,000)
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| Keywords | NMDA receptor / metabotropic glutamate receptor / cloning / molecular diversity / gene targeting / neuronal cell death / memory / neural information processing / グルタミン酸受容体 / メダボトロピック.グルタミン酸受容体 / 視覚系神経伝達 / 免疫組織化学 / 嗅覚系神経伝達 / 嗅覚記憶誘導 / 二次ニューロン / 受容体サブタイプ / 神経伝達制御 / イオン・チャンネル / 細胞内情報伝達系 / 発現分布 / 特異的アゴニスト / メタボトロピック受容体 / 発現部位 / 遺伝子ファミリ- / G蛋白共役受容体 |
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| Research Abstract |
Glutamate receptors can be classified into AMPA/kainate, NMDA and metabotropic (mGluR) receptors. The AMPA/kainate and NMDA receptors both act as glutamate-gated cation channels whereas mGluRs modulate the production of second messengers via G proteins. We have cloned and characterized the NMDA receptors and mGluRs with the aid of our cloning strategy that combines electrophysiology and a Xenopus oocyte expression system. We have elucidated the existence of diverse members of the NMDA receptors and mGluRs and have demonstrated the structures, properties and some crucial roles of these receptors in brain function. 1) The NMDA receptors consist of two distinct types of subunits : NMDAR1 possesses all properties characteristic of the NMDA receptors, whereas four NMDAR2 subunits confer functional variability of NMDA receptors by different heteromeric formations. 2) The mGluRs form a family of at least eight different subtypes (mGluR1-mGluR8) that can be classified into three subgroups according to their sequence similarities, signal transduction mechanisms, and agonist selectivities. 3) The specific up-regulation of NMDAR2A governs the NMDA receptor induction in granule cells during cerebellar development and plays an important role in granule cell survival and death. 4) mGluR6 is responsible for synaptic transmission from photoreceptors to ON-bipolar cells and mediates a key process in segregating visual signals into ON- and OFF- pathways. 5) mGluR2 at the presynaptic site of granule cells in the accessory olfactory bulb modulates inhibitory GABA transmission to mitral cells and plays an important role in discriminating olfactory stimuli and evoking an olfactory memory formation. These findings lead to an important concept that the second-odor neurons (mitral cells and bipolar cells) in the visual and olfactory sensory systems are essential in discriminating sensory transmission.
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