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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19100005/
• 关键词: シナプス回路; シナプス刈込み; グルタミン酸受容体; カルシウムイオン; シナプス; 脳; 発達; 小脳; 大脳皮質; バレル; カルシニューリン; 臨界期可塑性; CaMキナーゼ

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.

新生儿的突触回路的特点是多余的，重叠和纠缠的布线。这些未成熟的回路通过使用依赖性和活动依赖性的加强和弱化/消除未成熟的突触而被细化为功能性和成熟的回路。通过这个过程，几乎所有的高级大脑功能在出生后早期的敏感或关键时期都得到了有力的发展，包括人类的认知，语言，音乐表演，运动，智力，思想，个性和社会性。现在我们知道，活动依赖性突触回路的发展是由谷氨酸受体激活和随后的钙离子流入突触后神经元促进的。然而，很少有人知道钙离子内流如何调节竞争性突触发育。在这个研究项目中，我们的目的是澄清这个问题，重点是钙依赖性和非依赖性机制，使用神经解剖学，电生理学和发育生物学技术。通过这个研究项目，我澄清了P/Q型钙通道促进小脑浦肯野细胞的攀爬纤维神经支配的发展和成熟，而钙渗透性谷氨酸受体和转运蛋白调节体感皮层突触回路的发展。此外，GluD 2-Cbln 1-neurexin系统控制平行纤维-浦肯野细胞突触的连接，以与P/Q型钙通道促进的攀爬纤维神经支配竞争。

项目成果

Lack of molecular-anatomical machineries for GABAergic synaptic transmission at the axon initial segment of Cerebellar Purkinje cells

小脑浦肯野细胞轴突起始段缺乏 GABA 能突触传递的分子解剖机制

• 发表时间: 2011
• 作者: 岩倉淳;内ヶ島基政;渡辺雅彦
• 通讯作者: 渡辺雅彦

Evidence against GABA release from glutamatergic mossy fiber terminals in the developing hippocampus

发育中的海马体中谷氨酸能苔藓纤维末端释放 GABA 的证据

• 发表时间: 2007
• 期刊: Journal of Neuroscience 27
• 作者: Uchigashima;M. ;et. al.
• 通讯作者: et. al.

The SK2-long isoform directs synaptic localization and function of SK2-containing channels.

• DOI: 10.1038/nn.2832
• 发表时间: 2011-06
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Allen, Duane;Bond, Chris T.;Lujan, Rafael;Ballesteros-Merino, Carmen;Lin, Mike T.;Wang, Kang;Klett, Nathan;Watanabe, Masahiko;Shigemoto, Ryuichi;Stackman, Robert W., Jr.;Maylie, James;Adelman, John P.
• 通讯作者: Adelman, John P.

Acute cocaine exposure weakens GABA(B) receptor-dependent G-protein-gated inwardly rectifying K+ signaling in dopamine neurons of the ventral tegmental area.

• DOI: 10.1523/jneurosci.0494-11.2011
• 发表时间: 2011-08-24
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Arora D;Hearing M;Haluk DM;Mirkovic K;Fajardo-Serrano A;Wessendorf MW;Watanabe M;Luján R;Wickman K
• 通讯作者: Wickman K

Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity

• DOI: 10.1038/sj.emboj.7601639
• 发表时间: 2007-04-04
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Kakizawa, Sho;Kishimoto, Yasushi;Takeshima, Hiroshi
• 通讯作者: Takeshima, Hiroshi