| Project/Area Number |
09044324
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
MIYAMOTO Eishichi Kumamoto University, School of Medicine, Pharmacology, Professor, 医学部, 教授 (50109659)
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| Co-Investigator(Kenkyū-buntansha) |
MULLER Dominique Universite de Geneve, Faculte de Medecine, Pharmacology, Professor, 医学部, 教授
SODERLING Th オレゴン健康科学大学, ボラム研究所, 教授
KASAHARA Jiro Kumamoto University, School of Medicine, Pharmacology, Instructor, 医学部, 助手 (10295131)
YAMAMOTO Hideyuki Kumamoto University, School of Medicine, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)
FUKUNAGA Kohji Kumamoto University, School of Medicine, Pharmacology, Associate Professor, 医学部, 助教授 (90136721)
SODERLING Thomas R Oregon Health Sciences University, Vollum Institute, Professor
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | long-term potentiation / hippocampus / learning / memory / CaM kinase II / MAP kinase / protein phosphatase / protein dephosphorylation / シナプス伝達長期増強 / 後シナプス細胞 / 蛋白質燐酸化反応 / 遺伝子発現 |
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| Research Abstract |
The purposes of the study is to elucidate the mechanisms of learning and memory of animals on the basis of molecular cytobiological methodology. When electrical high frequency stimulation (HFS) is given to synapses, potentiation of synaptic activities lasts for several hours or longer. This phenomenon is called long-term potentiation(LTP) and considered to be a model for learning and memory of animals. The elucidation of the mechanisms of LTP will give a clue to understand the higher activity of the brain. It has been recently reported that protein phosphorylatiorr especially Ca^2/calmodulin-dependent protein kinaseII (CaM kinase II) is involved in induction and maintenance of LTP in the hippocampus. In an attempt to examine the molecular mechanisms of LTP in the hippocampus, we analyzed LTP.
1)Activation of CaM kinase II and mitogen-activated protein kinase (MAP kinase) was analyzed during LTP induction by the in-gel assay with myelin basic protein as a substrate. MAP kinase was activated during LTP induction. The peak of the activation was observed 3 min after HFS and rapidly decreased to the original level within 10 mm. When 50 muM PD098059, a MAP kinase kinase inhibitor, was previously given to hippocampal slices, LTP induction and activation of both CaM kinase II and MAP kinase were inhibited. However, addition of 30 muM PD098059 to slices did not affect both LTP and activation of CaM kinase II but did inhibit activation of MAP kinase. These results indication that LTP induction is correlated with activation of CaM kinase II, but not with activation of MAP kinase.
2)Calyculin A-sensitive protein phosphatase (PP) activity, which includes PP1 and PP2 was inhibited during LTP induction. The autoradiography and immunoblot analyses showed that phosphorylation of the regulatory subunit of PP2A is phosphorylated with a concomitant decrease in PP activity.
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