Molecular mechanisms for calcium-mediated refinement of competitive synaptic wiring in the brain

钙介导的大脑竞争性突触接线细化的分子机制

基本信息

批准号：
19100005
负责人：
WATANABE Masahiko
金额：
$ 74.8万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (S)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2011
项目状态：
已结题

项目摘要

Synaptic circuits in neonates are characterized by excess, overlapping and entangled wiring. These immature circuits are refined into functional and mature ones through use-dependent and activity-dependent strengthening and weakening/elimination of immature synapses. Through this process, almost all of higher brain functions develop robustly during sensitive or critical period of early postnatal life, including cognition, language, music performance, sports, intelligence, thought, personality, and sociality in the case of human beings. Now we understand that the activity dependent synaptic circuit development is facilitated by glutamate receptor activation and subsequent calcium influx into postsynaptic neurons. However little is known about how calcium influx regulates competitive synaptic development. In this research project, we aimed to clarify this issue by focusing on calcium-dependent and-independent mechanisms using neuroanatomical, electrophysiological, and developmental biological technologies. Through this research project, I clarified that P/Q-type calcium channels promote the development and maturation of climbing fiber innervation to Purkinje cells in the cerebellum, while calcium-permeable glutamate receptors and transporters regulate synaptic circuit development in the somatosensory cortex. Moreover, the GluD2-Cbln1-neurexin system controls the connectivity of parallel fiber-Purkinje cell synapses to compete with climbing fiber innervation promoted by P/Q-type calcium channels.

新生儿的突触电路的特征是过量，重叠和纠缠的布线。这些不成熟的电路通过使用依赖性和活性依赖性的增强和弱化/消除未成熟突触的功能和成熟电路。通过这一过程，几乎所有较高的大脑功能在产后早期生活的敏感或关键时期（包括认知，语言，音乐表现，体育，智力，思想，个性，个性和社会性）在人类的情况下都具有牢固的发展。现在，我们了解到，谷氨酸受体的激活和随后钙流入突触后神经元，促进了依赖活性的突触回路发育。然而，关于钙涌入如何调节竞争性突触发育的知之甚少。在该研究项目中，我们旨在通过使用神经解剖学，电生理和发育生物学技术专注于依赖钙依赖性和独立的机制来阐明这个问题。通过该研究项目，我澄清说，P/Q-Type钙通道促进了小脑中对Purkinje细胞的攀爬纤维神经支配的发展和成熟，而钙渗透性的谷氨酸受体和转运蛋白则调节体感皮质中突触的发育。此外，GLUD2-CBLN1-NEURXIN系统控制平行纤维 - 棕榈细胞突触的连通性，以与P/Q-Type钙通道促进的攀爬纤维神经竞争。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The endocannabinoid system is modulated in response to spinal cord injury in rats

DOI：
10.1016/j.nbd.2008.09.015
发表时间：
2009-01-01
期刊：
NEUROBIOLOGY OF DISEASE
影响因子：
6.1
作者：
Garcia-Ovejero, Daniel;Arevalo-Martin, Angel;Molina-Holgado, Eduardo
通讯作者：
Molina-Holgado, Eduardo

Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRd2

GluRd2 C 端 PDZ 结合基序对突触可塑性和小脑运动学习的差异调节

DOI：
发表时间：
2008
期刊：
J Neurosci 28
影响因子：
0
作者：
Kakegawa W;Miyazaki T;Emi K;Matsuda K;Kohda K;Motohashi J;Mishina M;Kawahara S;Watanabe M;Yuzaki M
通讯作者：
Yuzaki M

SK2 channel plasticity contributes to LTP at Shaffer collateral-CA1 synapses.

SK2 通道可塑性有助于 Shaffer 侧支 CA1 突触处的 LTP。