小脳抑制性シナプス可塑性の役割

• Project Area: Mesoscopic neurocircuitry: towards understanding of the functional and structural basis of brain information processing
• Project/Area Number: 25115716
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: 平野 丈夫 京都大学, 理学(系)研究科(研究院), 教授 (50181178)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 抑制性シナプス / シナプス可塑性 / 小脳 / プルキンエ細胞 / 運動学習 / 前庭動眼反射 / 視機性眼球運動

Outline of Annual Research Achievements

小脳は運動学習にかかわり、そこでのシナプス可塑性は運動学習の基盤と考えられる。中でも小脳皮質の平行線維・プルキンエ細胞間の興奮性シナプスで起こる長期抑圧(LTD)は、運動学習の基礎機構として注目されてきた。しかし、LTD阻害下で運動学習が起こる例が報告され、他の小脳シナプス可塑性の運動学習への関与が示唆された。本研究では、LTD障害を補い得るシナプス可塑性候補として、分子層介在神経細胞からプルキンエ細胞への抑制性シナプスで起こるRebound Potentiation(RP)と呼ばれる可塑性に注目した。LTDは興奮性シナプス伝達の抑制であり、一方RPは抑制性シナプス伝達の亢進であって、両者ともにプルキンエ細胞活動を抑える方向に作用する。また、両者は登上線維入力によって起こるプルキンエ細胞の脱分極により引き起こされるという共通性がある。そこで今回の研究で両者の誘導条件を検討したところ、同一のプルキンエ細胞刺激パターンにより、LTDもRPも誘導されることが明らかになった。
また、2013年度までの研究で、RP発現を特異的に抑制したトランスジェニックマウスを作製し、RPの行動制御上の役割を検討した。そして、このトランスジェニックマウスでは運動学習の一つである前庭動眼反射の適応が障害されているが、別の運動学習である視機性眼球運動の適応には異常が認められないことを示した（Tanaka et al., 2013）。これらの結果は、RPが一部の運動学習に特異的に関与していることを示唆している。そこで2014年度は、前庭動眼反射と視機性眼球運動の適応の関係を調べ、前庭動眼反射の適応訓練が視機性眼球運動に影響を及ぼすこと、両者の制御にアドレナリン受容体が異なる関与をすることを示す知見を得た。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Opposite regulation of sustained CaMKII activity by alpha and beta subunits impacts inhibitory synaptic plasticity. (2014)
  • Author(s): Nagasaki, N., Hirano, T. and Kawaguchi, S.
  • Journal Title: J. Physiol. Volume: 592 Issue: 22 Pages: 4891-4909
  • DOI: 10.1113/jphysiol.2014.280230
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Around LTD hypothesis in motor learning. (2014)
  • Author(s): Hirano, T.
  • Journal Title: Cerebellum Volume: 12 Issue: 5 Pages: 645-650
  • DOI: 10.1007/s12311-014-0581-4
  • NAID: 120005669284
  • Peer Reviewed
• [Journal Article] Control of spontaneous Ca2+ transients is critical for neuronal maturation in the developing neocortex. (2014)
  • Author(s): Y. Bando, K. Irie, T. Shimomura, H. Umeshima, Y. Kushida, M. Kengaku, Y. Fujiyoshi, T. Hirano and Y. Tagawa
  • Journal Title: Cerebral Cortex Volume: 1 Issue: 1 Pages: 1-12
  • DOI: 10.1093/cercor/bhu180
  • Peer Reviewed / Open Access
• [Journal Article] Live-cell imaging of receptors around postsynaptic membrane formed on adhesion-protein-coated glass (2014)
  • Author(s): Tanaka, H., Fujii, S. & Hirano, T.
  • Journal Title: Nature Protocols Volume: 9 Issue: 1 Pages: 76-89
  • DOI: 10.1038/nprot.2013.171
  • Peer Reviewed
• [Journal Article] Regulation and functional roles of rebound potentiation at cerebellar stellate cell - Purkinje cell synapse (2014)
  • Author(s): Hirano, T. & Kawaguchi, S.
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 8 Pages: 1-8
  • DOI: 10.3389/fncel.2014.00042
  • NAID: 120005385884
  • Peer Reviewed
• [Journal Article] Contribution of postsynaptic GluD2 to presynaptic R-type Ca2+ channel function, glutamate release and long-term potentiation at parallel fiber to Purkinje cell synapses (2013)
  • Author(s): Yamashita, M., Kawaguchi, S. & Hirano, T.
  • Journal Title: Cerebellum Volume: 12 Issue: 5 Pages: 657-666
  • DOI: 10.1007/s12311-013-0474-y
  • NAID: 120005575262
  • Peer Reviewed
• [Journal Article] Long-term potentiation of inhibitory synaptic transmission onto cerebellar Purkinje neurons contributes to adaptation of vestibulo-ocular reflex (2013)
  • Author(s): Tanaka, S., Kawaguchi, S. Shioi, G. & Hirano, T.
  • Journal Title: J. Neurosci. Volume: 33 Issue: 43 Pages: 17209-17220
  • DOI: 10.1523/jneurosci.0793-13.2013
  • NAID: 120005342657
  • Peer Reviewed
• [Journal Article] Long-term depression and other synaptic plasticity in the cerebellum (2013)
  • Author(s): Hirano, T.
  • Journal Title: Proceedings of the Japan Academy, Series B Volume: 89 Issue: 5 Pages: 183-195
  • DOI: 10.2183/pjab.89.183
  • NAID: 130003365114
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed
• [Journal Article] Dysfunction of KCNK potassium channels impairs neuronal migration in the developing mouse cerebral cortex. (2012)
  • Author(s): Yuki Bando
  • Journal Title: Cerebral Cortex Volume: in press Issue: 4 Pages: 1017-1029
  • DOI: 10.1093/cercor/bhs387
  • Peer Reviewed
• [Presentation] LTD and motor learning (2015)
  • Author(s): Hirano, T.
  • Organizer: 7th International symposium of the society for research on the cerebellum
  • Place of Presentation: Brussels
  • Year and Date: 2015-05-10
  • Invited
• [Presentation] Molecular mechanisms and roles of synaptic plasticity. (2015)
  • Author(s): Hirano, T.
  • Organizer: 1st Kyoto University and UC San Diego Joint Symposium, Section “Changing Brain”.
  • Place of Presentation: Kyoto
  • Year and Date: 2015-03-11
  • Invited
• [Presentation] Inhibitory synaptic plasticity in cerebellar Purkinje neurons and its differential contribution to motor learning paradigms. (2014)
  • Author(s): Hirano, T.
  • Organizer: Symposium “Synaptic regulation in the cerebellum and motor control” in the 37th annual meeting of the Japan Neuroscience Society
  • Place of Presentation: Yokohama
  • Year and Date: 2014-09-11
  • Invited
• [Presentation] Cerebellar inhibitory synaptic plasticity, rebound potentiation, contributes to adaptation of vestibulo-ocular reflex
  • Author(s): Tanaka, S., Kawaguchi, S. and Hirano, T.
  • Organizer: The 43rd Annual Meeting, Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] Regulation of neural activity is critical for the control of neural migration and dendrite formation of cortical layer 2/3 neurons in vivo
  • Author(s): Bando, Y., Irie, K., Kushida, Y., Shimomura, T., Fujiysohi, Y., Hirano, T. and Tagawa, Y.
  • Organizer: The 43rd Annual Meeting, Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] 「学習と記憶」のメカニズム
  • Author(s): 平野丈夫
  • Organizer: 千里ライフサイエンスフォーラム
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Visualized dynamics of glutamate receptors around postsynaptic membrane
  • Author(s): Hirano, T., Tanaka, H. and Fujii, S.
  • Organizer: Workshop “Molecular architecture and regulation mechanism of synapses” in the 36th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Kobe
  • Invited
• [Presentation] Visualization of glutamate receptors around postsynaptic membrane during synaptic plasticity
  • Author(s): Hirano, T.
  • Organizer: The 2nd Kyoto-Bristol Symposium 2014, Neuroscience Section
  • Place of Presentation: Kyoto
  • Invited
• [Presentation] Regulation mechanism and functional role of inhibitory synaptic plasticity in a cerebellar Purkinje neuron
  • Author(s): Hirano, T.
  • Organizer: Symposium “Mechanism and role of inhibitory synaptic plasticity” in the 91st Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Kagoshima
  • Invited
• [Presentation] Subtype-specific trafficking of AMPA receptors during hippocampal LTD
  • Author(s): Fujii, S., Tanaka, H. and Hirano, T.
  • Organizer: The 36th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Kyoto
• [Presentation] Regulation of excitability is critical for the control of migration and dendrite formation in the developing cerebral cortex
  • Author(s): Bando, Y., Irie, K., Kushida, Y., Shimomura, T., Fujiysohi, Y., Hirano, T. and Tagawa, Y.
  • Organizer: The 36th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Kyoto
• [Remarks] 小脳による運動学習・運動制御機構
  • URL: http://www.neurosci.biophys.kyoto-u.ac.jp/behavior.html
• [Remarks] 平野研究室ホームページ
  • URL: http://www.neurosci.biophys.kyoto-u.ac.jp/main.html
• [Remarks] 運動学習の新メカニズム解明に成功
  • URL: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2013_1/131023_1.htm