1996 Fiscal Year Final Research Report Summary
Studies of neural functions of the higher animals by the gene targeting analyzes
| Project/Area Number |
06454707
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
SUGIYAMA Hiroyuki Kyushu University, Faculty of Science, Department of Biology, Professor, 理学部, 教授 (20124224)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Isao Kyushu University, Faculty of Science, Department of Biology, Associate Professo, 理学部, 助教授 (20183741)
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| Project Period (FY) |
1994 – 1996
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| Keywords | gene targeting / glutamate receptor / long-term potentiation / NMDA receptor / learning / memory |
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| Research Abstract |
The goal of this project is to analyze the molecular mechanisms of neural fuctions of the higher animals (mice) by the method of targeted disruption of the genes for important neuronal molecules. Especially glutamate receptors of the NMDA type were focused, and the mice lacking the receptor subuints were examined (collaboration with Dr.Mishina, Tokyo University).
1.When the gene for the NMDA receptor epsilon1 subunit was disrupted in the mice, the long-term potentiation (LTP) in the CA1 region of hippocampal slices was significantly reduced. The mutant mice also showed reduced ability for the spatial learning. The results strongly suggested that the hippocampal LTP may be an important basis for the learning and memory.
2.The effects of the e1 disruption were studied during the postnatal development of the mice. NMDA receptor channel currents decreased with the age in both wild-type and mutant mice, but the values in the mutant mice were approximately half of those of the wild-type mice at all ages examined. In contrast, the LTP in the mutant mice was reduced in an age-dependent manner. The reduction was marginal at the neonate, and became progressively prominent, with the potentiation being 26% of that of the wild-type mice at the adulthood.
3.The effects of the epsilon1 disruption and the epsilon2 (another NMDA receptor subunit) disruption were compared at two distinct synaptic inputs in individual neurons in the CA3 region of hippocampal slices. The two types of gene disruptions caused different effects at the two synapses, suggesting that NMDA receptors with different subunit compositions may function in different synapses within a single CA3 pyramidal neuron.
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