1997 Fiscal Year Final Research Report Summary
Physiological Roles of the NMDA Receptor Channel in Brain Function
| Project/Area Number |
08458260
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Brain Research Institute, Niigata University |
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Principal Investigator |
SAKIMURA Kenji Brain Research Institute, Niigata University, Department of Cellular Neurobiology, Professor, 脳研究所, 教授 (40162325)
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| Project Period (FY) |
1996 – 1997
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| Keywords | NMDA receptor channel / Conditional gene targeting / Knockout mouse / Brain function / Synapse formation / Motor learning |
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| Research Abstract |
The NMDA receptor channel is unique in that its gating is governed by both ligands and voltage and is highly permeable to Ca^<2+>. These characteristics of the NMDA receptor channel are directly related to its important physiological roles in synaptic plasticity as a molecular coincidence detector. Some forms of long-term potentiation and long-term depression, which are thought to underlie learning, memory and neural network formation, are dependent on the NMDA receptor channel. Four epsilon subunits are known as major determinants of the diversity of the NMDA receptor channel. To investigate the physiological significance of its diversity, we generated mutant mice defective in the four epsilon subunits. The following results were obtained by analyzes of the mutant mice.
1) The mutant mice defective in both epsilon1 and epsilon3 subunits showed moderate defects in learning motor skills, suggesting that the NMDA receptor channel is involved in motor learning.
2) The auditory startle response was raised in the epsilon4 subunit knockout adult mice. This phenomenon may reflect modification of a neural circuit of auditory startle reflex. The epsilon4 subunit may be related to formation of the neural circuit.
3) Allodynia which is induced by prostaglandin disappeared by double mutation of epsilon1 and epsilon4, showing that the NMDA-mediated pathway is important for prostaglandin-induced nociception.
4) It was clarified that different synaptic targeting of NMDA receptor subunits occurred at hippocampal synapses corresponding to each epsilonsubunit.
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