Control of critical period development in mouse somatosensory cortex by glutamatergic signal transduction

谷氨酸信号转导控制小鼠体感皮层关键期发育

• 批准号: 17300108
• 负责人: WATANABE Masahiko
• 金额: $ 9.6万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17300108/
• 关键词: glutamate; receptor; barrel; plasticity; critical period; 可塑性; グルタミン酸受容体; グルタミン酸トランスポーター; 体性感覚野; 大脳皮質; 発達; 遺伝子ノックアウトマウス

In the present study, I studied on the molecular mechanisms regulating critical period development of the mouse somatosensory cortex using gene knockout mice. In particular, I focused on the roles played by NMDA-type glutamate receptor subunits GluRe2 (NR2B) and GLuRe4 (NR2D) and also by glutamate transporter GLAST and GLT1 in developmental appearance, critical period termination, critical period plasticity of somatosensory barrel structures. Here I found that, compared to wild-type control mice, heterozygous GlnRe2+/-mice showed one-day retardation in developmental appearance and critical period termination, whereas homozygous GluRe4-/-mice did on-day facilitation. No significant change was seen in the magnitude of critical period plasticity, as determined by row-C whisker cautery. In contrast, homozygous GLAST-/-and GLTI-/-mice displayed significant reduction in the magnitude of critical period plasticity, with normal developmental appearance and critical period termination. These results provide experimental evidence that N3IDA receptor activation regulates temporal properties of somatosensory development in a subunit-dependent manner, while transporters regulating extracellular glutamate concentration magnify critical period plasticity. Therefore, armed with the two mechanisms, synaptic refinement during development is shaped normally in a activity-dependent manner.

在本研究中，我利用基因敲除小鼠研究了调节小鼠体感觉皮层发育关键期的分子机制。我特别关注了nmda型谷氨酸受体亚基GluRe2 （NR2B）和GLuRe4 （NR2D）以及谷氨酸转运体GLAST和GLT1在体感桶状结构发育外观、关键期终止和关键期可塑性中的作用。这里我发现，与野生型对照小鼠相比，杂合GlnRe2+/-小鼠在发育外观和关键期终止方面表现为一天延迟，而纯合GluRe4-/-小鼠则表现为一天促进。通过行- c晶须烧灼法测定，临界期塑性的大小没有明显变化。纯合子GLAST-/和GLTI-/-小鼠的关键期可塑性显著降低，发育外观正常，关键期终止。这些结果为N3IDA受体激活以亚基依赖的方式调节体感觉发育的时间特性提供了实验证据，而转运体调节细胞外谷氨酸浓度放大了关键时期的可塑性。因此，有了这两种机制，发育过程中的突触细化以活动依赖的方式正常形成。

项目成果

Number and density of AMPA receptors in individual synapses in the cerebellum as revealed by SDS-digested freeze-fracture replical labeling.

通过 SDS 消化的冷冻断裂复制标记显示小脑单个突触中 AMPA 受体的数量和密度。

• 发表时间: 2007
• 期刊: J. Neurosci. (in press)
• 作者: Masugi-Tokita M;Tarusawa E;Watanabe M;Molnar E;Fujimoto K;Shigemoto R
• 通讯作者: Shigemoto R

Effects of RNA interference of Atg4B on the limited proteolysis of LC3 in PC12 cells an expression of Ata4B in various rat tissues.

Atg4B RNA 干扰对 PC12 细胞中 LC3 有限蛋白水解和各种大鼠组织中 Ata4B 表达的影响。

• 发表时间: 2006
• 期刊: Autophagy 2
• 作者: Yoshimura K;Shibata M;Koike M;Gotoh K;Fukaya M;Watanabe M;Uchiyama Y
• 通讯作者: Uchiyama Y

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

Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain

• DOI: 10.1111/j.1471-4159.2006.03835.x
• 发表时间: 2006-06-01
• 期刊: JOURNAL OF NEUROCHEMISTRY
• 影响因子: 4.7
• 作者: Miura, Eriko;Fukaya, Masahiro;Watanabe, Masahiko
• 通讯作者: Watanabe, Masahiko

Differential Roles of Glial and Neuronal Glutamate Transporters in Purkinje Cell Synapses

• DOI: 10.1523/jneurosci.1020-05.2005
• 发表时间: 2005-09
• 期刊: The Journal of Neuroscience
• 作者: Y. Takayasu;M. Iino;W. Kakegawa;H. Maeno;K. Watase;K. Wada;D. Yanagihara;T. Miyazaki;O. Komine;Masahiko Watanabe;Kohichi Tanaka;S. Ozawa