| Project/Area Number |
05404085
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | University of Tokyo (1994)
Niigata University (1993) |
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Principal Investigator |
MISHINA Masayoshi University of Tokyo, Faculty of Medicine, Professor, 医学部(医), 教授 (80144351)
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| Co-Investigator(Kenkyū-buntansha) |
SAKIMURA Kenji Niigata University, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (40162325)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 1994: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1993: ¥14,400,000 (Direct Cost: ¥14,400,000)
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| Keywords | NMDA receptor channel / epsilon1 subunit / Synaptic plasticity / Long-term potentiation / Spatial learning / Gene targeting / Hippocampus / Synaptic plasticity hypothesis of memory and learning / 記憶 / 学習 / シナプス形成 / 遺伝子ノックアウト / ES細胞 |
|---|
| Research Abstract |
The N-methyl-D-aspartate (NMDA) receptor channel plays a key role in synaptic plasticity, which is thought to underlie learning, memory and development. The NMDA receptor channel is formed by at least two members of the glutamate receptor (GluR) channel subunit families, that is, the GluRepsilon and GluRzeta subunit families. The four epsilon subunits are distinct in distribution, properties and regulation. Based on the Mg^<2+> sensitivity and expression patterns, we have proposed that the epsilon1 and epsilon2 subunits play a role in synaptic plasticity. Here we show that targeted disruption of the mouse epsilon1 subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation (LTP) at the hippocampal CA1 synapses. The mutant mice also showed moderate deficiency in spatial learning. These results support the notion that the NMDA receptor channel-dependent synaptic plasticity is the cellular basis of certain forms of learning.
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