Elucidation of molecular mechanisms for the regulation of metaplasticity of synaptic transmission

2009 Fiscal Year Final Research Report

• Project/Area Number: 17023011
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: MANABE Toshiya The University of Tokyo, 医科学研究所, 教授 (70251212)
• Project Period (FY): 2005 – 2009
• Keywords: 脳・神経 / 生理学 / 神経科学 / シグナル伝達 / 遺伝子

Research Abstract

In this project, we have elucidated the mechanisms of the regulation of long-term potentiation (LTP) by muscarinic acetylcholine receptors in the hippocampus as well as the regulation of morphological and functional plasticity by intracellular protein kinases. We have also discovered the novel type of LTP in the hippocampal CA1 region that is non-Hebbian and dependent on postsynaptic Ca^<2+> channels. In the hippocampal CA3 region, we have elucidated the mechanisms for the proper trajectory of mossy fibers and for the regulation of mossy fiber excitability in new-born mice. In the lateral nucleus of the amygdala, we have found that the NMDA receptor GluN2B subunit is involved in excitatory synaptic transmission and its plasticity and that tyrosine phosphorylation of this subunit is associated with LTP induction and expression as well as the formation of fear memory at the whole-animal level.

Research Products

• [Journal Article] Non-Hebbian synaptic plasticity induced by repetitive postsynaptic action potentials (2009)
  • Author(s): Kato, H.K., Watabe, A.M., Manabe, T.
  • Journal Title: J. Neurosci. 29 Pages: 11153-11160
• [Journal Article] Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons. (2009)
  • Author(s): Fukushima, F., Nakao, K., Shinoe, T., Fukaya, M., Marumatsu, S. -i., Sakimura, K., Kataoka, H., Mori, H., Watanabe, M, Manabe, T., Mishina, M.
  • Journal Title: PLoS ONE 4 Pages: e3993
• [Journal Article] Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation (2009)
  • Author(s): Inoue, N., Nakao, H., Migishima, R., Hino, T., Matsui, M., Hayashi, F., Nakao, K., Manabe, T., Aiba, A., Inokuchi, K.
  • Journal Title: Mol. Brain 2 Pages: 7
• [Journal Article] Kinase-dead knock-in mouse reveals an essential role of Ca2+/calmodulin-dependent protein kinase IIα kinase activity in dendritic spine enlargement, LTP and learning. (2009)
  • Author(s): Yamagata, Y., Kobayashi, S., Umeda, T., Inoue, A., Sakagami, H., Fukaya, M., Watanabe, M., Hatanaka, N., Totsuka, M., Yagi, T., Obata, K., Imoto, K., Yanagawa, Y., Manabe, T., Okabe, S.
  • Journal Title: J. Neurosci. 29 Pages: 7607-7618
• [Journal Article] Involvement of NMDAR2A tyrosine phosphorylation in depression-related behavior (2009)
  • Author(s): Taniguchi, S., Nakazawa, T., Tanimura, A., Kiyama, Y., Tezuka, T., Watabe, A. M., Katayama, N., Yokoyama, K., Inoue, T., Izumi-Nakaseko, H., Kakuta, S., Sudo, K., Iwakura, Y., Umemori, H., Inoue, T., Murphy, N. P., Hashimoto, K., Kano, M., Manabe, T., Yamamoto, T.
  • Journal Title: EMBO J. 28 Pages: 3717-3729
• [Journal Article] Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and LTP induction in the adult mouse CNS (2008)
  • Author(s): Miwa, H., Fukaya, M., Watabe, A.M., Watanabe, M., Manabe, T.
  • Journal Title: J. Physiol. (Lond. ) 586 Pages: 2539-2550
• [Journal Article] Use-dependent amplification of presynaptic Ca2+ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse (2008)
  • Author(s): Shimizu, H., Fukaya, M., Yamasaki, M., Watanabe, M., Manabe, T., Kamiya, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 11998-12003
• [Journal Article] Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release (2008)
  • Author(s): Sakisaka, T., Yamamoto, Y., Mochida, S., Nakamura, M., Nishikawa, K., Ishizaki, H., Okamoto-Tanaka, M., Miyoshi, J., Fujiyoshi, Y., Manabe, T., Takai, Y.
  • Journal Title: J. Cell Biol. 183 Pages: 323-337
• [Journal Article] Upregulated PAR-2-mediated salivary secretion in mice deficient in muscarinic acetylcholine receptor subtypes (2007)
  • Author(s): Nishiyama, T., Nakamura, T., Obara, K., Inoue, H., Mishima, K., Matsumoto, N., Matsui, M., Manabe, T., Mikoshiba, K., Saito, I.
  • Journal Title: J. Pharmacol. Exp. Ther. 320 Pages: 516-524
• [Journal Article] Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum (2007)
  • Author(s): Narushima, M., Uchigashima, M., Fukaya, M., Matsui, M., Manabe, T., Hashimoto, K., Watanabe, M., Kano, M.
  • Journal Title: J. Neurosci. 27 Pages: 496-506
• [Journal Article] GABAergic interneurons facilitate mossy fiber excitability in the developing hippocampus (2007)
  • Author(s): Nakamura, M., Sekino, Y., Manabe, T.
  • Journal Title: J. Neurosci. 27 Pages: 1365-1373
• [Journal Article] Interactions between plexin-A2, plexin-A4 and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers (2007)
  • Author(s): Suto, F., Tsuboi, M., Kamiya, H., Mizuno, H., Kiyama, Y., Komai, S., Shimizu, M., Sanbo, M., Yagi, T., Hiromi, Y., Chedotal, A., Mitchell, K.J., Manabe, T., Fujisawa, H.
  • Journal Title: Neuron 53 Pages: 535-547
• [Journal Article] The neuropeptide nociceptin is a synaptically released endogenous inhibitor of hippocampal long-term potentiation (2007)
  • Author(s): Bongsebandhu-phubhakdi, S., Manabe, T.
  • Journal Title: J. Neurosci. 27 Pages: 4850-4858
• [Journal Article] Involvement of protein-tyrosine phosphatase PTPMEG in motor learning and cerebellar long-term depression (2007)
  • Author(s): Kina, S. -i., Tezuka, T., Kusakawa, S., Kishimoto, Y., Kakizawa, S., Hashimoto, K., Ohsugi, M., Kiyama, Y., Horai, R., Sudo, K., Kakuta, S., Iwakura, Y., Iino, M., Kano, M., Manabe, T., Yamamoto, T.
  • Journal Title: Eur. J. Neurosci. 26 Pages: 2269-2278
• [Journal Article] Involvement of nectins in the formation of puncta adherentia junctions and the mossy fiber trajectory in the mouse hippocampus (2006)
  • Author(s): Honda, T., Sakisaka, T., Yamada, T., Kumazawa, N., Hoshino, T., Kajita, M., Kayahara, T., Ishizaki, H., Tanaka-Okamoto, M., Mizoguchi, A., Manabe, T., Miyoshi, J., Takai, Y.
  • Journal Title: Mol. Cell. Neurosci. 31 Pages: 315-325
• [Journal Article] NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity (2006)
  • Author(s): Nakazawa, T., Komai, S., Watabe, A.M., 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.
  • Journal Title: EMBO J. 25 Pages: 2867-2877
• [Journal Article] The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse urinary bladder (2005)
  • Author(s): Ehlert, F.J., Griffin, M.T., Abe, D.M., Vo, T.H., Taketo, M.M., Manabe, T., Matsui, M.
  • Journal Title: J. Pharmacol. Exp. Ther. 313 Pages: 368-378
• [Journal Article] Roles of M2 and M4 muscarinic receptors in regulating acetylcholine release from myenteric neurons of mouse ileum (2005)
  • Author(s): Takeuchi, T., Fujinami, K., Goto, H., Fujita, A., Taketo, M.M., Manabe, T., Matsui, M., Hata, F.
  • Journal Title: J. Neurophysiol. 93 Pages: 2841-2848
• [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, A.M., Rump, A., Tanaka, M., Suda, Y., Kato, S., Morikawa, Y., Manabe, T., Miyajima, A.
  • Journal Title: Mol. Cell. Biol. 25 Pages: 4166-4175
• [Journal Article] Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus (2005)
  • Author(s): Shinoe, T., Matsui, M., Taketo, M.M., Manabe, T.
  • Journal Title: J. Neurosci. 25 Pages: 11194-11200
• [Presentation] Cholinergic suppression of synaptic transmission in the lateral amygdala. (2009)
  • Author(s): Tazuke, C., Miwa, H., Matsui, M., Watabe, A.M., Manabe, T.
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: Annual Meeting in Nagoya, Japan
  • Year and Date: 2009-09-17
• [Presentation] Prolonged low-frequency stimulation induces mitochondria-dependent short-term potentiation at hippocampal CA3-CA1 synapses (2009)
  • Author(s): Morimoto, T., Watabe, A.M., Manabe, T.
  • Place of Presentation: International Congress of Physiological Sciences in Kyoto
  • Year and Date: 2009-07-28
• [Presentation] Calcium influx through voltage-dependent calcium channels can induce non-Hebbian LTP in the CA1 region of the mouse hippocampus (2008)
  • Author(s): Kato, H., Watabe, A.M., Manabe, T.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Annual Meeting in Washington DC, U.S.A.
  • Year and Date: 2008-11-17
• [Presentation] Hippocampal long-term potentiation is inhibited by synaptically released endogenous nociceptin (2008)
  • Author(s): Bongsebandhu-phubhakdi, S., Manabe, T.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Annual Meeting in Washington DC, U.S.A.
  • Year and Date: 2008-11-17
• [Presentation] Synaptic vesicle pool size affects the frequency dependency of synaptic transmission in the hippocampus (2008)
  • Author(s): Fukushima, A., Sekino, Y., Manabe, T.
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: Annual Meeting in Tokyo, Japan
  • Year and Date: 2008-07-09
• [Presentation] Calcium influx through voltage-dependent calcium channels can induce non-Hebbian long-term potentiation in the hippocampus (2008)
  • Author(s): Kato, H., Watabe, A.M., Manabe, T.
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: Annual Meeting in Tokyo, Japan
  • Year and Date: 2008-07-09
• [Presentation] Presynaptic mechanisms of the frequency-dependent depression at perforant path-granule cell synapses in the hippocampus (2008)
  • Author(s): Fukushima, A., Sekino, Y., Manabe, T.
  • Organizer: The Physiological Society of Japan
  • Place of Presentation: The 85th Annual Meeting in Tokyo, Japan
  • Year and Date: 2008-03-26
• [Presentation] Functional properties of the NMDA receptor in the lateral amygdala: comparison with those in the hippocampal CA1 region. Symposium "Cellular and molecular mechanism of synaptic plasticity" (The Physiological Society of (2007)
  • Author(s): Miwa, H., Fukaya, M., Watabe, A., Watanabe, M., Manabe, T.
  • Organizer: The Physiological Society of Japan
  • Place of Presentation: The 84th Annual Meeting in Osaka, Japan
  • Year and Date: 2007-03-20
• [Presentation] Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors (2006)
  • Author(s): Shinoe, T., Matsui, M., Manabe, T.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Annual Meeting in Atlanta, U.S.A.
  • Year and Date: 2006-10-16
• [Presentation] Inhibitory modulation of synaptic plasticity is stronger in the dentate gyrus than in the CA1 region of the hippocampus. (2006)
  • Author(s): Arima, F., Watabe, A.M., Manabe, T.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Annual Meeting in Atlanta, U.S.A.
  • Year and Date: 2006-10-14
• [Presentation] Presynpatic GABAA receptors modulate frequency facilitation at developing hippocampal mossy fiber synapses (2006)
  • Author(s): Nakamura, M., Sekino, Y., Manabe, T.
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: Annual Meeting in Kyoto, Japan
  • Year and Date: 2006-07-20
• [Presentation] Inhibitory modulation of synaptic plasticity is stronger in the dentate gyrus than in the CA1 (2005)
  • Author(s): Arima, F., Manabe, T.
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: Annual Meeting in Yokohama, Japan
  • Year and Date: 2005-07-26
• [Presentation] Roles of presynaptic TrkB receptors in synaptic plasticity in the hippocampal CA1 region (2005)
  • Author(s): Kumazawa, N., Kato, E., Matsushiro, H., Takeuchi, T., Mishina, M., Manabe, T.
  • Organizer: The Physiological Society of Japan
  • Place of Presentation: The 82nd Annual Meeting in Sendai, Japan
  • Year and Date: 2005-05-19
• [Presentation] The role of tyrosine phosphorylation of NMDA receptors in higher brain functions (2005)
  • Author(s): Manabe, T.
  • Organizer: Symposium "From NMDA receptors to higher brain functions and dysfunction treatments"
  • Place of Presentation: The 78th Annual Meeting of the Japanese Pharmacological Society in Yokohama, Japan
  • Year and Date: 2005-03-24
• [Book] 分子基盤からみた学習機構の生後発達「脳科学と学習・教育」 (2010)
  • Author(s): 真鍋俊也
  • Total Pages: 179-189
  • Publisher: 明石書店
• [Book] 長期増強「現代医学・生物学の仮説・学説2008」生体の科学第59巻5号 (2008)
  • Author(s): 真鍋俊也
  • Total Pages: 430-431
  • Publisher: 医学書院
• [Book] 海馬におけるシナプス可塑性「分子・細胞・シナプスからみる脳」 (2008)
  • Author(s): 真鍋俊也古市貞一(編)
  • Total Pages: 216-230
  • Publisher: 東京大学出版会
• [Book] Associative Long-Term Potentiation.(edited by Binder, M.D., Hirokawa, N., Windhorst, U., In: Encyclopedia of Neuroscience) (2008)
  • Author(s): Manabe, T.
  • Total Pages: 194-195
  • Publisher: Springer
• [Book] Long-Term Potentiation (LTP).(edited by Binder, M.D., Hirokawa, N., Windhorst, U., In: Encyclopedia of Neuroscience) (2008)
  • Author(s): Manabe, T.
  • Total Pages: 2188-2190
  • Publisher: Springer
• [Book] Memory, Molecular Mechanisms(edited by Binder, M.D., Hirokawa, N., Windhorst, U., In: Encyclopedia of Neuroscience) (2008)
  • Author(s): Manabe, T.
  • Total Pages: 2319-2320
  • Publisher: Springer
• [Book] シナプス可塑性(長期増強、長期抑圧、構造変化)(森寿、真鍋俊也、渡辺雅彦、岡野栄之、宮川剛(編), 脳神経科学イラストレイテッド, 改訂代2版) (2006)
  • Author(s): 渡部文子、真鍋俊也
  • Total Pages: 181-187
  • Publisher: 羊土社
• [Book] 脳機能研究の新展開(狩野方伸、高田昌彦、伊佐正(編), 扁桃体におけるシナプス可塑性と情動記憶の分子メカニズム 実験医学増刊) (2006)
  • Author(s): 真鍋俊也
  • Total Pages: 159-163
  • Publisher: 羊土社
• [Book] 遺伝子制御による選択的シナプス強化・除去機構の解明(狩野方伸(編), 海馬シナプスの修飾機構におけるシナプス機能分子の役割) (2005)
  • Author(s): 真鍋俊也
  • Total Pages: 69-94
  • Publisher: クパブロ
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/NeuronalNetwork/Neuronal_Network/Index_japanese.htm