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INPUT-SELECTIVE SORTING OF THE NMDA RECEPTOR SUBUNITS IN MOUSE HIPPOCAMPAL PYRAMIDAL NEURONS.

小鼠海马锥体神经元中 NMDA 受体亚基的输入选择性排序。

基本信息

批准号：
09680796
负责人：
ITO Isao
金额：
$ 1.98万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680796/
关键词：
HIPPOCAMPUS NMDA RECEPTOR ィイD2εィエD2 1 SUBUNIT ィイD2εィエD2 2 SUBUNIT SYNAPSE CA3 PYRAMIDAL NEURON CA1錐体細胞

项目摘要

Recently, by examining the effects of targeted disruption of the GluR ィイD2εィエD2 1(NR2A)and GluR ィイD2εィエD2 2(NR2B)subunits on NMDA receptor activities, we have shown that NMDA receptors operating at different CA3 pyramidal cell synapses might have different subunit compositions. In this project, we confirmed our previous observation by pharmacological analyses using Ro 25-6981 and ifenprodil, the GluR ィイD2εィエD2 2 subunit selective NMDA receptor antagonists. Next, we examined the effects of the GluR ィイD2εィエD2 1 subunit disruption on NMDA receptor-mediated currents in response to glutamate applied iontophoretically. NMDA receptor-mediated currents of the GluR ィイD2εィエD2 1 mutant mice were reduced to one-half that of the wild-type mice both in the apical dendrite and in the basal dendrite of CA3 pyramidal neurons. We also examined the postnatal developments of the long-term potentiation(LTP)in the CA3 region. The development of LTP at the CA3 stratum radiatum synapses closely followed the development of the GluR ィイD2εィエD2 1 subunit, and the GluR ィイD2εィエD2 1 mutation strongly suppressed this LTP. The LTP at the CA3 stratum oriens synapses was not affected significantly by the mutation at all ages. Then, we examined the effects of the GluR ィイD2εィエD2 1 subunit disruption on NMDA EPSCs at two types of synapses on the basal dendrites of CA3 pyramidal neurons. The GluR ィイD2εィエD2 1 subunit disruption resulted in a significant reduction of NMDA EPSCs in the commissural/associational-CA3 synapse, whereas NMDA EPSCs in the commissural-CA3 synapse were apparently unaffected. Our data indicate that synapse-selective sorting of the GluR ィイD2εィエD2 subunits is also found in the wild-type mice and that this targeted distribution is dependent on the types of synaptic input but not on the cell polarity.

最近，我们通过研究靶向破坏GluR受体NR 2A和NR 2B亚基对NMDA受体活性的影响，发现作用于不同CA 3锥体细胞突触的NMDA受体可能具有不同的亚基组成。在本项目中，我们通过使用Ro 25-6981和艾芬地尔（ifenprodil）的药理学分析证实了我们先前的观察，这两种药物是GluR β D 2 ε D 2 2亚基选择性NMDA受体拮抗剂。接下来，我们研究了谷氨酸受体D2ε受体D2 1亚基破坏对NMDA受体介导的电流的影响，这些电流响应于离子电渗施加的谷氨酸。在CA 3区锥体神经元的顶树突和基底树突上，GluR β 1 D2ε 1 D2 1突变小鼠的NMDA受体介导的电流减少到野生型小鼠的一半。我们还研究了出生后的发展的长时程增强（LTP）在CA 3区。CA 3辐射层突触LTP的发生与GluR β D2ε D2 1亚基的发生密切相关，GluR β D2ε D2 1突变强烈抑制LTP的发生。在CA 3层东方突触的LTP没有受到显着影响的突变在所有年龄。然后，我们研究了GluR β D 2 ε D 2 1亚基破坏对CA 3锥体神经元基底树突上两种类型突触的NMDA EPSC的影响。GluR β-D 2 ε-D 2 1亚基的破坏导致连合/联合-CA 3突触的NMDA EPSC显著减少，而连合-CA 3突触的NMDA EPSC明显不受影响。我们的数据表明，在野生型小鼠中也发现了GluR β D2ε D2亚基的突触选择性分选，并且这种靶向分布依赖于突触输入的类型，而不是细胞极性。