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皮层关键期发育的分子机制。我特别关注了 NMDA 型谷氨酸受体亚基 GluRe2 (NR2B) 和 GLuRe4 (NR2D) 以及谷氨酸转运蛋白 GLAST 和 GLT1 在体感桶结构的发育外观、关键期终止和关键期可塑性中所发挥的作用。在这里，我发现，与野生型对照小鼠相比，杂合子 GlnRe2+/- 小鼠在发育外观和关键期终止方面表现出一日迟缓，而纯合子 GluRe4-/- 小鼠则表现出一日促进。通过 C 排晶须烧灼测定，关键期可塑性的大小没有观察到显着变化。相比之下，纯合 GLAST-/- 和 GLTI-/- 小鼠的关键期可塑性显着降低，但发育外观和关键期终止正常。这些结果提供了实验证据，证明 N3IDA 受体激活以亚基依赖性方式调节体感发育的时间特性，而调节细胞外谷氨酸浓度的转运蛋白则放大关键期可塑性。因此，有了这两种机制，发育过程中的突触细化通常以活动依赖的方式形成。

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