Studies on activity-dependent maturation of synaptic function during postnatal cerebellar development

2009 Fiscal Year Final Research Report

• Project/Area Number: 17023021
• 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 (2007-2009); Osaka University (2005-2006)
• Principal Investigator: KANO Masanobu The University of Tokyo, 大学院・医学系研究科, 教授 (40185963)
• Co-Investigator(Kenkyū-buntansha): SAKIMURA Kenji 新潟大学, 脳研究所, 教授 (40162325) ; OKABE Shigeo 東京大学, 大学院・医学系研究科, 教授 (60204012)
• Project Period (FY): 2005 – 2009
• Keywords: 分子・細胞神経科学 / ニューロン・シナプス・神経回路 / 神経発生・神経発達・神経再生・神経再建 / 姿勢・運動制御

Research Abstract

This research aimed at elucidating the mechanisms underlying strengthening of necessary synaptic connections and elimination of redundant ones during postnatal development of the brain. For this purpose, we used climbing fiber to Purkinje cell synapses in the cerebellum as a model system. We have disclosed that postnatal development of climbing fiber to Purkinje cell synapse consists of four distinct phases : (1)functional differentiation, (2)dendritic translocation of a single climbing fiber, (3)early phase of synapse elimination, (4)late phase of synapse elimination. We have elucidated part of the molecular mechanisms underlying each of the four phases. Moreover, we have established an organotipic coculture preparation of cerebellar slices with medulla explants containing the inferior olive. In this preparation, formation and elimination of climbing fiber synapses occur in a manner similar to those seen in vivo. This preparation can be used for screening candidate molecules that may be involved in the development of climbing synapses. Through the five years' research, we have achieved most of the original purposes.

Research Products

• [Journal Article] Translocation of a "winner" climbing fiber to the Purkinje cell dendrite and subsequent elimination of "losers" from the soma in developing cerebellum (2009)
  • Author(s): Hashimoto, K, Ichikawa, R., Kitamura, K., Watanabe, M., Kano, M.
  • Journal Title: Neuron 63 Pages: 106-118
  • Peer Reviewed
• [Journal Article] Synapse elimination in the central nervous system (2009)
  • Author(s): Kano. M., Hashimoto, K.
  • Journal Title: Curr Opin Neurobiol 19 Pages: 154-161
  • Peer Reviewed
• [Journal Article] Influence of parallel fiber-Purkinje cell synapse formation on postnatal development of climbing fiber-Purkinje cell synapses (2009)
  • Author(s): Hashimoto, K., Yoshida, T., Sakimura, K., Mishina, M., Watanabe, M., Kano, M.
  • Journal Title: Neuroscience 162 Pages: 601-611
  • Peer Reviewed
• [Journal Article] Endocannabinoid-mediated control of synaptic transmission (2009)
  • Author(s): Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M., Watanabe, M.
  • Journal Title: Physiol. Rev. 89 Pages: 309-80
  • Peer Reviewed
• [Journal Article] Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long-term depression, endocannabinoid signalling and synapse elimination (2008)
  • Author(s): Kano, M., Hashimoto, K., Tabata, T.
  • Journal Title: Philos. Trans. R. Soc. Lond. B Biol. Sci. 363 Pages: 2173-2186
  • Peer Reviewed
• [Journal Article] Postsynaptic GABAB receptor signalling enhances LTD in mouse cerebellar Purkinje cells (2007)
  • Author(s): Kamikubo, Y., Tabata, T., Kakizawa, S., Kawakami, D., Watanabe, M., Ogura, A., Iino, M., Kano, M.
  • Journal Title: J. Physiol. 585 Pages: 549-563
  • Peer Reviewed
• [Journal Article] Endogenous cannabinoid signaling through the CB1 receptor is essential for cerebellum-dependent discrete motor learning (2006)
  • Author(s): Kishimoto, Y., Kano, M.
  • Journal Title: J. Neurosci. 26 Pages: 8829-8837
  • Peer Reviewed
• [Journal Article] Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain (2005)
  • Author(s): Kakizawa, S., Miyazaki, T., Yanagihara, D., Iino, M., Watanabe, M., Kano, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 102 Pages: 19180-19185
  • Peer Reviewed
• [Presentation] Activity-dependent regulation of climbing fiber synapse elimination during postnatal cerebellar development. Gordon Research Conference on Neural Circuits & Plasticity (2009)
  • Author(s): Kano, M.
  • Place of Presentation: Newport, RI, USA.
  • Year and Date: 2009-06-08
• [Presentation] Mechanisms of Ca2+-driven endocannabinoid release: A pharmacological and genetic approach (2007)
  • Author(s): Kano, M., Hashimotodani, Y., Ohno-Shosaku, T., Fukami, K.
  • Organizer: 17th Neuropharmacology Conference "Cannabinoid signaling in the nervous system. "
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2007-10-31
• [Book] Synaptic plasticity in the cerebellum.( Abel Lajtha (ed), K. Mikoshiba (Volume ed), In: Handbook of Neurochemistry and Molecular Neurobiology 3rd Edition Neural Signaling Mechanisms.) (2009)
  • Author(s): Tabata, T., Kano M.
  • Total Pages: 63-86
  • Publisher: Springer Sciencet Business Media, LLC
• [Book] 小脳におけるシナプス可塑性(甘利俊一/監修、古市貞一/編, シリーズ脳科学5、分子・細胞・シナプスからみる脳) (2008)
  • Author(s): 田端俊英、狩野方伸
  • Total Pages: 230-263
  • Publisher: 東京大学出版会
• [Remarks]
  • URL: http://plaza.umin.ac.jp/~neurophy/