| Project/Area Number |
07044281
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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 Institution | Kumamoto University |
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Principal Investigator |
MIYAMOTO Eishichi Kumamoto University, School of Medicine, Professor, 医学部, 教授 (50109659)
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| Co-Investigator(Kenkyū-buntansha) |
MULLER Dominique Geneva University (Switzerland), Professor, ジュネーブ大学・医学部, 教授
SODERLING Th アメリカ, オレゴン健康科学大学・ボラム研究所, 教授
YAMAMOTO Hideyuki Kumamoto University, School of Medicine, Assistant Professor, 医学部, 講師 (60191433)
FUKUNAGA Kohji Kumamoto University, School of Medicine, Associate Professor, 医学部, 助教授 (90136721)
SODERLING Thomas R Oregon Health Science University (USA), Professor
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| Project Period (FY) |
1995 – 1996
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| Keywords | Hippocampus / Synaptic long-term potentiation / Learning / Memory / Glutamate receptor / Ca^<2+>mobilization / CaM kinase II / Protein phospatases / Endogenous substrates |
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| Research Abstract |
High-frequency stimulation of afferents to certain synapses causes long-lasting potentiation of synaptic transmission efficacy in the hippocampus. This phenomenon is called long-term potentiation (LTP), which is a possible model for a cellular mechanism for learning and memory in vertebrate brain. Since the discovery of LTP,the molecular mechanisms responsible for the neurophysiological phenomena have been investigated in the hippocampus. Ca^<2+>-dependent protein kinases, especially, Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) is implicated in the induction of LTP in the hippocampus.
The present project elucidated the following findings 1) Application of high but not low frequency stimulation to tow groups of afferents in the CA1 region of ^<32>P-labeled slices resulted in autophosphorylation of CaM kinase IIalpha and beta subunits as well asphosphorylation of synapsin I and microtubule-associated protein 2 (MAP2) which are localized in the presynaptic and post-synap
… More
tic neurons, respectively. 2) The phosphorylation site of synapsin I was site II during LTP induction, which is the site phosphorylated by CaM kinase II.It indicates that activated CaM kinase II during LTP induction phosphorylates certain substrates in neurons. 3) Autophosphorylation of CaM kinase II and phosphorylation of synapsin I and MAP2 were inhibited by addition of AP5 which is an NMDA glutamate receptor antagonists. 4) Addition of calmidazolilum, a calmodulin antagonist, inhibited not only LTP induction, but also autophosphorylation of CaM kinase II alpha and beta subunits and phosphorylation of synapsin I and MAP2.5) Immunoblotting analysis revealed that LTP induction was associated with an increase in the amount of CaM kinase II beta subunit in the CA1 region. 6) Calyculin A-sensitive protein phosphatase activity decreased during LTP induction in association with phosphorylation of the regulatory subunit of protein phosphatase 2A.In vitro experiments revealed that the phosphorylation of the regulatory subunit of protein phosphatase 2A inhibit the activity of the enzyme. Less
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