Microglia Dependent Development of Neuronal Circuits in the Cerebellum

• Project/Area Number: 15K18342
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Hiroshima University
• Principal Investigator: Nakayama Hisako 広島大学, 医歯薬保健学研究院(医), 助教 (70397181)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ミクログリア / 小脳 / 神経回路形成 / 発達 / プルキンエ細胞 / 登上線維 / シナプス再編成 / シナプス刈り込み

Outline of Final Research Achievements

We investigated whether microglia was crucial for the development of cerebellar neuronal circuits We studied whether and how microglia contribute to climbing fiber (CF) synapse elimination in the developing cerebellum. By ablating microglia from the developing cerebellum pharmacologically and genetically, we found that microglia was needed for CF synapse elimination during the second postnatal week. We observed almost no sign of microglia engulfing CFs, suggesting that microglia contribute to CF synapse elimination in a mechanism other than phagocytosis. Instead, synapses which have been reported to be crucial for the CF synapse elimination were affected in transgenic mice with reduced microglia. These results suggest that microglia contribute to CF synapse elimination through regulating synaptic input to Purkinje cells.

Research Products

• [Journal Article] Ionic Basis for Membrane Potential Resonance in Neurons of the Inferior Olive. (2016)
  • Author(s): Matsumoto-Makidono, Y., Nakayama, H., Yamasaki, M., Miyazaki, T., Kobayashi, K., Watanabe, M., Kano, M., Sakimura, K., Hashimoto, K.
  • Journal Title: Cell Reports Volume: 16 Issue: 4 Pages: 994-1004
  • DOI: 10.1016/j.celrep.2016.06.053
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis. (2016)
  • Author(s): Miyake K, Ohta T, Nakayama H, Doe N, Terao Y, Oiki E, Nagatomo I, Yamashita Y, Abe T, Nishikura K, Kumanogoh A, Hashimoto K, Kawahara Y.
  • Journal Title: Cell Reports Volume: 17 Issue: 8 Pages: 2004-2014
  • DOI: 10.1016/j.celrep.2016.10.073
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A CDC42EP4/septin-based perisynaptic glial scaffold facilitates glutamate clearance. (2015)
  • Author(s): Ageta-Ishihara N, Yamazaki M, Konno K, Nakayama H, Abe M, Hashimoto K, Nishioka T, Kaibuchi K, Hattori S, Miyakawa T, Tanaka K, Huda F, Hirai H, Hashimoto K, Watanabe M, Sakimura K, Kinoshita M.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 10090-10090
  • DOI: 10.1038/ncomms10090
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 神経細胞のResonance特性に関わるイオンチャネルの解析 (2017)
  • Author(s): 橋本浩一、槇殿佳子、中山寿子、山崎美和子、宮崎太輔、小林和人、渡辺雅彦、狩野方伸、崎村建司
  • Organizer: 第94回 日本生理学会大会
  • Place of Presentation: 浜松市
  • Year and Date: 2017-03-28
• [Presentation] Genetic manipulation of mTORC1 signaling in mouse cerebellar Purkinje cell. (2016)
  • Author(s): Kassai, H., Sakai, Y., Nakayama, H., Maeda, T., Hashimoto, K., Kano, M., Aiba, A.
  • Organizer: Neuroscience 2016 annual meeting Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] 細胞膜Resonance特性に関わるイオンチャネル (2016)
  • Author(s): 橋本浩一、槇殿佳子、中山寿子
  • Organizer: 第68回 日本生理学会 中国四国地方会
  • Place of Presentation: 岡山市
  • Year and Date: 2016-11-05
• [Presentation] Ion channels responsible for the resonant property of neurons in the inferior olive (2016)
  • Author(s): 橋本浩一、中山寿子、松本佳子
  • Organizer: 第59回 日本神経化学会大会
  • Place of Presentation: 福岡市
  • Year and Date: 2016-09-08
• [Presentation] Spatial and temporal distribution of microglia and climbing fiber-Purkinje cell synapses during postnatal cerebellar development (2015)
  • Author(s): Nakayama Hisako, Chie Morimoto, Ryo Takimoto, Kouichi Hashimoto
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県・神戸市）
  • Year and Date: 2015-07-28
• [Presentation] Functional roles of microglia in postnatal refinement of the cerebellar circuit (2015)
  • Author(s): Hisako Nakayama and Kouichi Hashimoto
  • Organizer: 新学術領域研究「グリアアセンブリによる脳機能発現の制御と病態」第2回夏の（国際）ワークショップ
  • Place of Presentation: 岡崎コンファレンスセンター（愛知県・岡崎市）
  • Year and Date: 2015-07-10
  • Int'l Joint Research