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，我研究了使用基因基因敲除小鼠调节小鼠体感皮质的关键时期发展的分子机制。特别是，我专注于NMDA型谷氨酸受体亚基Glure2（NR2B）和Glure4（NR2D）以及谷氨酸转运蛋白GLAST和GLT1在发育外观，关键周期终止，关键周期终止，关键周期性周期可变性中的作用。在这里，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周期终止中显示一日迟缓，而纯合glure4 - / - 小鼠在当今的促进中确实进行了促进。通过行-C晶须捕捉确定的关键周期可塑性的大小，没有看到显着变化。相比之下，纯合胶水 - / - 和glti - / - 小鼠在关键周期可塑性的幅度上显示出显着降低，并具有正常的发育外观和关键的周期终止。这些结果提供了实验证据，表明N3IDA受体激活以亚基依赖性方式调节体感发展的时间特性，而调节细胞外谷氨酸浓度的转运蛋白会放大关键周期可塑性。因此，用这两种机制武装，发育过程中的突触改进以活性依赖性方式正常形成。

项目成果

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

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

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

通过 SDS 消化的冷冻骨折复制品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. 27
• 作者: Masugi-Tokita M;Tarusawa E;Watanabe M;Molnar E;Fujimoto K;Shigemoto R
• 通讯作者: Shigemoto R

Gene expression and localization of diacylglycerol kinase isozymes in the rat spinal cord and dorsal root ganglia.

大鼠脊髓和背根神经节中二酰甘油激酶同工酶的基因表达和定位。

• 发表时间: 2006
• 期刊: Cell Tissue Res. 326
• 作者: Sasaki H;Hozumi Y;Hasegawa H;Ito T;Takagi M;Ogino T;Watanabe M;Goto K
• 通讯作者: Goto K

The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic site in the hippocampus and cerebellum.

CB1 大麻素受体是海马和小脑兴奋性突触前位点的主要大麻素受体。

• 发表时间: 2006
• 期刊: J. Neurosci. 26
• 作者: Kawamura Y;Fukaya M;Maejima T;Yoshida T;Miura E;Watanabe M;Ohno-Shosaku T;Kano M
• 通讯作者: Kano M