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

出生后小脑发育过程中突触功能活动依赖性成熟的研究

• 批准号: 17023021
• 负责人: KANO Masanobu
• 金额: $ 160.7万
• 依托单位: The University of Tokyo (2007-2009)Osaka University (2005-2006)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17023021/
• 关键词: 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; 神経科学; シグナル伝達; シナプス; 発達; 脳・神経; 小脳; プルキンエ細胞; 登上線維

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.

本研究旨在阐明出生后大脑发育过程中必要的突触连接加强和多余的突触连接消除的机制。为此，我们使用小脑中的爬行纤维到浦肯野细胞突触作为模型系统。我们发现，攀缘纤维到浦肯野细胞突触的发育经历了四个不同的阶段：（1）功能分化，（2）单个攀缘纤维的树突转位，（3）突触消除的早期阶段，（4）突触消除的晚期阶段。我们已经阐明了这四个阶段的部分分子机制。此外，我们还建立了小脑切片与含有下橄榄的髓质外植体的器官共培养制备。在这种制备中，攀缘纤维突触的形成和消除以类似于体内观察到的方式发生。该制剂可用于筛选可能参与攀爬突触发育的候选分子。经过五年的研究，我们达到了最初的大部分目的。

项目成果

Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice.

• DOI: 10.1093/hmg/ddn403
• 发表时间: 2009-02-15
• 期刊: Human molecular genetics
• 影响因子: 3.5
• 作者: Sato T;Miura M;Yamada M;Yoshida T;Wood JD;Yazawa I;Masuda M;Suzuki T;Shin RM;Yau HJ;Liu FC;Shimohata T;Onodera O;Ross CA;Katsuki M;Takahashi H;Kano M;Aosaki T;Tsuji S
• 通讯作者: Tsuji S

Tonic enhancement of endocannabinoid-mediated retrograde suppression of inhibition by cholinergic interneuron activity in the striatum

• DOI: 10.1523/jneurosci.4644-06.2007
• 发表时间: 2007-01-17
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Narushima, Madoka;Uchigashima, Motokazu;Kano, Masanobu
• 通讯作者: Kano, Masanobu

A Novel Form of Memory for Auditory Fear Conditioning at a Low-Intensity Unconditioned Stimulus

• DOI: 10.1371/journal.pone.0004157
• 发表时间: 2009-01-09
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Kishioka, Ayumi;Fukushima, Fumiaki;Mishina, Masayoshi
• 通讯作者: Mishina, Masayoshi

Involvement of NMDAR 2 A tyrosine phosphorylation in depression-related behavior

• 发表时间: 2009
• 作者: S. Taniguchi;A. Tanimura;Y. Kiyama;T. Tezuka;A. M. Watabe;Norikazu Katayama;Kazumasa Yokoyama;Takeshi Inoue;Hiroko Izumi‐Nakaseko;S. Kakuta;K. Sudo;Y. Iwakura;H. Umemori;Takafumi Inoue;N. Murphy;K. Hashimoto;M. Kano;T. Manabe;Tadashi Yamamoto

Requirement of type 1 metabotropic glutamate receptor for activity-dependent synapse elimination in the lateral geniculate nucleus

外侧膝状核中活动依赖性突触消除需要 1 型代谢型谷氨酸受体

• 发表时间: 2008
• 作者: Narushima-Takahashi M