1993 Fiscal Year Final Research Report Summary
Molecular pharmacological studies on the expression of synaptic plasticity
| Project/Area Number |
04670124
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
FUKUNAGA Kohji Kumamoto University, Pharmacology, Associate Professor, 医学部, 助教授 (90136721)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Hideyuki Kumamoto University, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)
MIYAMOTO Eishichi Kumamoto University, Pharmacology, Professor, 医学部, 教授 (50109659)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Hippocampus / Memory / Learning / Synaptic long-term potentiation / Glutamate receptor / NMDA receptor / Ca^<2+> mobilization / CaM kinase II / 蛋白質燐酸化反応 |
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| Research Abstract |
Long-term potentiation (LTP) is a form of synaptic plasticity widely investigated as a molecular basis of the memory formation. Studies on several protein kinase inhibitors have indicated a role of Ca^<2+>/calmodulin-dependent protein kinase II(CaM kinase II) in LTP of hippocampus. We hypothesized that elevation of intracellular Ca^<2+> through NMDA receptor activation would trigger autophosphorylation of CaM kinase II to form its Ca^<2+>-independent species, which would remain active even when the intracellular Ca^<2+> was resequestered to its basal level. In cultured hippocampal neurons, activation of NMDA receptor increased the Ca^<2+>-independent activity of CaM kinase II and in turn stimulated the phosphorylation of target proteins such as microtuble-associated protein 2 and synapsin I.Furthermore, high frequency stimulation applied to Cal afferents in the hippocampal slices resulted in the induction of LTP with concomitant long-lasting increases in the Ca^<2+>-independent and total CaM kinase II activities as well as an increases in the ratio of Ca^<2+>-independent to total activity. The effect was obtained using two different CaM kinase II substrates, syntide 2 and synapsin I, and it was observed in hippocampal slices and hippocampal organotypic cultures. The treatment of slices with NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate prevent LTP induction and abolished the increase in the Ca^<2+>-independent activity as well as the increase in the total activity. These finding suggest that CaM kinase II can act as an important molecule for the formation of the hippocampal LTP.
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