Mechanism of climbing fiber synapse elimination at the developing Purkinje cell bodies

• Project/Area Number: 24790185
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Hokkaido University
• Principal Investigator: MIYAZAKI Taisuke 北海道大学, 医学(系)研究科(研究院), 助教 (90374230)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: プルキンエ細胞 / ルガロ細胞 / バスケット細胞 / 登上線維

Research Abstract

In the developing cerebellum, climbing fiber (CF)-Purkinje cell (PC) synapses are eliminated from PC cell bodies, while the maturation of inhibitory interneurons such as basket (BC) or Lugaro cells (LC) proceeds. It has been unclear whether these excitatory and inhibitory inputs are directly correlated or not. In the present study, we investigated the process of CF-PC synapses elimination from PC cell bodies when the inhibitory interneurons are functionally disrupted. By analyses using with lentivirus and GFP-expressing reporter mouse, we found that somatic CF terminals were expelled by developing BC axons. In contrast to PC somata, CF terminals beneath PC layer increased in number during the second postnatal week, and CFs from multiple neuronal origins were found to innervate the somatodendritic domain of single LCs. Thus, the elimination of somatic CFs appears to proceed with the differentiation of inhibitory neuronal elements.

Research Products

• [Journal Article] Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors (2013)
  • Author(s): Ohkawa T, Fukata Y, Yamasaki M, Miyazaki T, Yokoi N, Takashima H, Watanabe M, Watanabe O, Fukata M
  • Journal Title: J Neurosci. Volume: 33(46) Pages: 18161-74
  • Peer Reviewed
• [Journal Article] Disruption of cerebellar microzonal organization in GluD2 (GluRδ2) knockout mouse (2013)
  • Author(s): Hashizume M, Miyazaki T, Sakimura K, Watanabe M, Kitamura K, Kano M
  • Journal Title: Front Neural Circuits Volume: 7 Pages: 130-130
  • Peer Reviewed
• [Journal Article] Type 2 K(+) -Cl(-) cotransporter is preferentially recruited to climbing fiber synapses during development and the stellate cell-targeting dendritic zone at adulthood in cerebellar Purkinje cells (2013)
  • Author(s): Kawakita I, Uchigashima M, Konno K, Miyazaki T, Yamasaki M, Watanabe M
  • Journal Title: Eur J Neurosci. Volume: 37(4) Pages: 532-43
  • Peer Reviewed
• [Journal Article] Disruption of cerebellar microzonal organization in GluD2 (GluRd2) knockout mouse. (2013)
  • Author(s): Hashizume M, Miyazaki T, Sakimura K, Watanabe M, Kitamura K, Kano M
  • Journal Title: Front Neural Circuits Volume: 7 Pages: 130-130
  • DOI: 10.3389/fncir.2013.00130
  • Peer Reviewed
• [Journal Article] Antibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors. (2013)
  • Author(s): Ohkawa T, Fukata Y, Yamasaki M, Miyazaki T, Yokoi N, Takashima H, Watanabe M, Watanabe O, Fukata M
  • Journal Title: J Neurosci, Volume: 33 Issue: 46 Pages: 18161-18174
  • DOI: 10.1523/jneurosci.3506-13.2013
  • Peer Reviewed
• [Journal Article] Type 2 K+ -Cl- cotransporter ispreferentially recruited to climbingfiber synapses during development andthe stellate cell-targeting dendriticzone at adulthood in cerebellar Purkinje cells (2013)
  • Author(s): Kawakita I, Uchigashima M, Konno K, Miyazaki T, Yamasaki M, Watanabe M
  • Journal Title: Eur J Neurosci Volume: 37(4) Issue: 4 Pages: 532-43
  • DOI: 10.1111/ejn.12076
  • Peer Reviewed
• [Journal Article] Three types of neurochemical projection from the bed nucleus of the stria terminalis to the ventral tegmental area in adult mice (2012)
  • Author(s): Kudo T, Uchigashima M, Miyazaki T, Konno K, Yamasaki M, Yanagawa Y, Minami M, Watanabe M
  • Journal Title: J Neurosci. Volume: 32(50) Pages: 18035-46
  • NAID: 120005295651
  • Peer Reviewed
• [Journal Article] Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation (2012)
  • Author(s): Ito-Ishida A, Miyazaki T, Miura E, Matsuda K, Watanabe M, Yuzaki M, Okabe S
  • Journal Title: Neuron Volume: 76(3) Pages: 549-64
  • Peer Reviewed
• [Journal Article] Lack of molecular-anatomical evidence for GABAergic influence on axon initial segment of cerebellar Purkinje cells by the pinceau formation (2012)
  • Author(s): Iwakura A, Uchigashima M, Miyazaki T, Yamasaki M, Watanabe M
  • Journal Title: J Neurosci. Volume: 32(27) Pages: 9438-48
  • NAID: 120005090597
  • Peer Reviewed
• [Journal Article] GABAergic inhibition regulates developmental synapse elimination in the cerebellum (2012)
  • Author(s): Nakayama H, Miyazaki T, Kitamura K, Hashimoto K, Yanagawa Y, Obata K, Sakimura K, Watanabe M, Kano M
  • Journal Title: Neuron Volume: 74(2) Pages: 384-96
  • Peer Reviewed
• [Journal Article] Three types of neurochemical projection from the bed nucleus of the stria terminalis to the ventral tegmental area in adult mice. (2012)
  • Author(s): Kudo T, Uchigashima M, Miyazaki T, Konno K, Yamasaki Y, Yanagawa Y, Minami M, Watanabe M
  • Journal Title: J. Neurosci. Volume: 32 Issue: 50 Pages: 18035-18046
  • DOI: 10.1523/jneurosci.4057-12.2012
  • NAID: 120005295651
  • Peer Reviewed
• [Journal Article] Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation (2012)
  • Author(s): Ito-Ishida, A., Miyazaki, T., Miura, E., Matsuda, K., Watanabe, M., Yuzaki, M and S. Okabe
  • Journal Title: Neuron Volume: 76 Issue: 3 Pages: 549-564
  • DOI: 10.1016/j.neuron.2012.07.027
  • Peer Reviewed
• [Journal Article] Lack ofmolecular-anatomical evidence forGABAergic influence on axon initialsegment of cerebellar Purkinje cells by the pinceau formation (2012)
  • Author(s): Iwakura A, Uchigashima M, Miyazaki T,Yamasaki M, Watanabe M
  • Journal Title: J Neurosci Volume: 32(27) Issue: 27 Pages: 9438-48
  • DOI: 10.1523/jneurosci.1651-12.2012
  • Peer Reviewed
• [Journal Article] GABAergic inhibition regulates developmental synapse elimination in the cerebellum. (2012)
  • Author(s): Nakayama H
  • Journal Title: Neuron Volume: 74 Issue: 2 Pages: 384-396
  • DOI: 10.1016/j.neuron.2012.02.032
  • Peer Reviewed
• [Presentation] Morphological analysis of cerebellar interneuron Lugaro cells using with GFP expressing transgenic mice line (2013)
  • Author(s): Miyazaki T, Tanaka KF, Kohda K, Yuzaki M, Watanabe M
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館【京都】
• [Presentation] 蛍光タンパク発現モデルマウスを用いた小脳ルガロ細胞の形態学 (2013)
  • Author(s): 宮崎太輔、山崎美和子、渡辺雅彦
  • Place of Presentation: サンポート高松【香川】
• [Presentation] Morphological analysis of cerebellar interneuron Lugaro cells using with GFP–expressing transgenic mice line (2013)
  • Author(s): Taisuke Miyazaki, Kenji F. Tanaka, Kazuhisa Kohda, Michisuke Yuzaki, Masahiko Watanabe
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] 蛍光タンパク発現モデルマウスを用いた小脳ルガロ細胞の形態学 (2013)
  • Author(s): 宮崎 太輔、山崎 美和子、渡辺 雅彦
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: サンポート高松（香川）
• [Presentation] Elimination of somatic climbing fiber synapses proceeds with the differentiation of cerebellar interneurons (2012)
  • Author(s): Miyazaki T., Kohda K., Tanaka KF, Yuzaki M, Yanagawa Y., Watanabe M
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場【愛知】
• [Presentation] Elimination of somatic climbing fiber synapses proceeds with the differentiation of cerebellar interneurons. (2012)
  • Author(s): Taisuke Miyazaki, Kazuhisa Kohda, Kenji F. Tanaka, Michisuke Yuzaki, Yuchio Yanagawa, Masahiko Watanabe
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場（愛知）