2007 Fiscal Year Final Research Report Summary
Modulation of NMDA receptors and its role in synaptic plasticity
| Project/Area Number |
17500204
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | The University of Tokyo |
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Principal Investigator |
WATABE Ayako The University of Tokyo, Institute of Medical Science, Assistant Professor (00334277)
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| Project Period (FY) |
2005 – 2007
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| Keywords | LTP / NMDA receptors / Amygdala / Hippocampus / mGluR / Learning and Memory / Emotion / リン酸化 |
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| Research Abstract |
Long-term potentiation (LTP) at excitatory synapses in the hippocampus and amygdala is considered to be a cellular mechanism underlying neural plasticity such as memory and learning. The N-methyl-D-aspartate type of glumatate receptor (NMDAR) plays a key role in the induction of LTP as well as learning. Phosphorylation-dependent changes in NMDAR function have a crucial role in dynamic modulation of neural circuitry. The NR2B subunit of the NMDAR is tyrosine-phosphorylated in the brain, with Tyr-1472 its major phosphorylation site. Mice with a knockin mutation of the Tyr-1472 site to phenylalanine (Y1472F) show that Tyr-1472 phosphorylation is essential for fear learning and amygdaloid synaptic plasticity. The knockin mice show impaired fear-related learning and reduced amygdaloid long-term potentiation. NMDA receptor-mediated CaMKII signaling is impaired in YF/YF mice. Electron microscopic analyses reveal that the Y1472F mutant of the NR2B subunit shows improper localization at synapses in the amygdala. Thus, Tyr-1472 phosphorylation is a key mediator of fear learning and amygdaloid synaptic plasticity. Next, functional properties of NR2B subunit-containing receptors were studied in the amygdala and the Cal region of the hippocampus. We have found that the NR2B subunit significantly contributes to synaptic transmission, and its contribution is greater in the LA than in the Cal region, and biophysical properties of NMDA receptors and the NR2B/NR2A ratio are different between the two brain regions. These results indicate that NR2B subunit-containing NMDA receptors accumulate on the synaptic site and responsible for the unique properties of synaptic function and plasticity in the amygdala.
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Research Products
(15 results)
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[Journal Article] NR2B tyrosine phosphorylation modulates fear learing as well as amygdaloid naptic plasticity2006
Author(s)
Nakazawa T*, Komai S*, Watabe AM*, Kiyama Y, Fukaya M, Arima-Yoshida F, Horai R, Sudo K, Ebine K, Delawary M, Goto J, Umemori H, Tezuka T, Iwakura Y, Watanabe M, Yamamoto T & Manabe T. (*These authors contributed equally to this work)
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Journal Title
EMBO Journal 25
Pages: 2867-2877
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] (These authors contributed equally to this work) NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity2006
Author(s)
Nakazawa T, Komai S, Watabe AM, Kiyama Y, Fukaya M, Arima-Yoshida F, Horai R, Sudo K, Ebine K, Delawary M, Goto J, Umemori H, Tezuka T, Iwakura Y, Watanabe M, Yamamoto T & Manabe T.
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Journal Title
EMBO Journal 25
Pages: 2867-2877
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neuronal leucine-rich repeat protein 4 functions in hippocampus-dependent long-lasting memory.2005
Author(s)
Bando T, Sekine K, Kobayashi S, Watabe AM, Rump A, Tanaka M, Suda Y, Kato S, Morikawa Y, Manabe T, Miyajimsa A.
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Journal Title
Molecular and Cellular Biology 25
Pages: 4166-4175
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Neuronal leucine-rich repeat protein 4 functions in hippocampus-dependent long-lasting memory2005
Author(s)
Bando T, Sekine K, Kobayashi S, Watabe AM, Rump A, Tanaka M, Suda Y, Kato S, Morikawa Y, Manabe T, Miyajima A.
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Journal Title
Molecular and Cellular Biology 25
Pages: 4166-4175
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The presynaptic TrkB receptor modulates an N-type Ca2+ channel-dependent component of post-tetanic potetiation2006
Author(s)
Kumazawa, N., Kato, E., Takeuchi, T., Watebe, A. M., Mishina, M., Manabe, T.
Organizer
36th Annual Meeting of the Society for Neuroscience
Place of Presentation
Atlanta. U. S. A
Year and Date
20061014-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] NR2B tyrosine-phosphorylation modulates fear learning and NMDAR localization at synapses2006
Author(s)
Watabe A. M., Nakazawa T., Komai S., Kiyama Y., Fukaya M., Arima F., Watanabe M., Yamamoto T., and Manabe T.
Organizer
Gordon Research Conference, Neural Circuits and Plasticity
Place of Presentation
Salve Regina University Newport, RI, USA
Year and Date
20060626-0701
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The presynaptic TrkB receptor modulates an N-type Ca2+ channel-dependent component of post-tetanic potetiation.2006
Author(s)
Kumazawa, N., Kato, E., Takeuchi, T., Watebe, A. M., Mishina, M., Manabe, T.
Organizer
北米神経科学会
Place of Presentation
アトランタ
Year and Date
2006-10-15
Description
「研究成果報告書概要(和文)」より
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