Construction and system analaysis of cultured neuronal circuit with learning ability

• Project/Area Number: 15KT0082
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Constructive Systems Biology
• Research Institution: Kyoto University (2017-2018); Doshisha University (2015-2016)
• Principal Investigator: Kawaguchi Shin-ya 京都大学, 産官学連携本部, 特定准教授 (00378530)
• Research Collaborator: SAKABA Takeshi
• Project Period (FY): 2015-07-10 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 神経細胞 / シナプス / イメージング / 膜電位 / 可塑性 / 軸索 / パッチクランプ / 培養神経回路 / 学習 / シナプス可塑性 / 神経回路 / 可視化 / 蛍光イメージング / 光刺激 / 自己組織化 / 培養神経細胞 / 人工知能 / 培養細胞

Outline of Final Research Achievements

To fully understand the plasticity of neuronal circuit underlying the learning and memory in animals, we need a technique that enables large scale recordings of multiple neuronal activity and/or functional changes of synapses at the same time. For this aim, here I have developed a fluorescent imaging probe for membrane potential that reports neuronal activities in real-time. Voltage imaging enabled to observe spatio-temporal pattern of neuronal circuit and its plastic changes.
In addition, combined application of fluorescent imaging technique and sub-cellular patch-clamp method have clarified mechanisms of plasticity at various synapses in the cerebellar circuit.

Academic Significance and Societal Importance of the Research Achievements

記憶や学習がいかなる神経回路の情報処理変化によりもたらされるかを理解することは、認知症など高次脳機能障害の原因・対処法に繋がる基盤となる。本研究で得られた神経細胞の活動を大規模に観測することを可能にする革新的光技術と、神経回路の柔軟性を生みだす細胞・分子レベルでのメカニズムについての知見は、神経系の作動原理の理解を深化させ、さらに将来の発展につながる基礎となるものと言える。

Research Products

• [Int'l Joint Research] Paris Descartes University/CNRS(フランス)
• [Int'l Joint Research] CNRS(フランス)
• [Journal Article] Synaptic m6A Epitranscriptome Reveals Functional Partitioning of Localized Transcripts for Dynamic Tripartite Synapse Modulation. (2018)
  • Author(s): Merkurjev, D., Hong, W. T., Iida, K., Oomoto, I., Goldie, B. J., Yamaguti, H., Ohara, T. Kawaguchi, S. Y., Hirano, T., Martin, K. C., Pellegrini, M. & Wang, D. O.
  • Journal Title: Nature Neuroscience Volume: 21 Issue: 7 Pages: 1004-1014
  • DOI: 10.1038/s41593-018-0173-6
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Vesicular GABA Uptake Can Be Rate Limiting for Recovery of IPSCs from Synaptic Depression. (2018)
  • Author(s): Yamashita M, Kawaguchi SY, Hori T, Takahashi T.
  • Journal Title: Cell Reports Volume: 22 Issue: 12 Pages: 3134-3141
  • DOI: 10.1016/j.celrep.2018.02.080
  • NAID: 120006425878
  • Peer Reviewed / Open Access
• [Journal Article] Axonal GABAA receptors depolarize presynaptic terminals and facilitate transmitter release in cerebellar Purkinje cells. (2017)
  • Author(s): Zorrilla de San Martin J, Trigo FF, Kawaguchi SY.
  • Journal Title: The Journal of Physiology Volume: 595 Issue: 24 Pages: 7477-7493
  • DOI: 10.1113/jp275369
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fast Ca2+ Buffer-Dependent Reliable but Plastic Transmission at Small CNS Synapses Revealed by Direct Bouton Recording. (2017)
  • Author(s): Kawaguchi SY, Sakaba T.
  • Journal Title: Cell Reports Volume: 21 Issue: 12 Pages: 3338-3345
  • DOI: 10.1016/j.celrep.2017.11.072
  • Peer Reviewed / Open Access
• [Journal Article] Ca(2+) current facilitation determines short-term facilitation at inhibitory synapses between cerebellar Purkinje cells. (2015)
  • Author(s): Francois Diaz-Rojas, Takeshi Sakaba, Shin-ya Kawaguchi
  • Journal Title: The Journal of Physiology Volume: 593 Issue: 22 Pages: 4889-4904
  • DOI: 10.1113/jp270704
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Control of Synaptic Outputs by Dynamic Axonal Excitability (2019)
  • Author(s): Shin-ya Kawaguchi
  • Organizer: 9th FAOPS Congress
  • Int'l Joint Research / Invited
• [Presentation] 小脳神経回路における軸索・シナプス前部での動的情報処理 (2018)
  • Author(s): 川口 真也
  • Organizer: 第41回 日本神経科学大会
  • Invited
• [Presentation] Experimental and model analysis of transmitter release mechanisms at small presynaptic terminals in the CNS (2017)
  • Author(s): Shin-ya Kawaguchi
  • Organizer: 日本生理学大会
  • Place of Presentation: アクトシティ浜松（静岡県浜松市）
  • Year and Date: 2017-03-30
  • Invited
• [Presentation] Regulatory mechanism of transmitter release at a small presynaptic terminal. (2017)
  • Author(s): 川口真也
  • Organizer: 日本神経科学大会
  • Invited
• [Presentation] Biophysics and short-term plasticity in cerebellar small presynaptic terminals (2016)
  • Author(s): Shin-ya Kawaguchi
  • Organizer: JSPS & OIST Joint Symposium
  • Place of Presentation: OIST（沖縄県恩納村）
  • Year and Date: 2016-09-26
  • Int'l Joint Research / Invited
• [Presentation] Short-term facilitation is predominantly mediated by presynaptic Ca2+ current facilitation at Purkinje cell - Purkinje cell synapses (2015)
  • Author(s): Francois Diaz-Rojas, Takeshi Sakaba, Shin-ya Kawaguchi
  • Organizer: 北米神経科学会大会 sfn2015
  • Place of Presentation: 米国 シカゴ
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] 軸索終末での活動電位調節による短期シナプス可塑性 (2015)
  • Author(s): 川口真也、坂場武史
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-07-29