Control of Synaptic Connection by Glutamate Receptor δ2 in the Adult Cerebellum

Control of Synaptic Connection by Glutamate Receptor δ2 in the Adult Cerebellum
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DOI:
10.1523/jneurosci.4740-04.2005
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发表时间:
2005-02
期刊:
The Journal of Neuroscience
影响因子:
--
通讯作者:
T. Takeuchi;T. Miyazaki;Masahiko Watanabe;H. Mori;K. Sakimura;M. Mishina
T. Takeuchi;T. Miyazaki;Masahiko Watanabe;H. Mori;K. Sakimura;M. Mishina
中科院分区:
其他
文献类型:
--
作者:
T. Takeuchi;T. Miyazaki;Masahiko Watanabe;H. Mori;K. Sakimura;M. Mishina

文献摘要

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突触前和突触后特化的精确拓扑匹配是有效突触传递的必要条件。此外,突触连接在整个生命过程中都受到重排的影响。在C57BL/6纯遗传背景下,通过诱导型和小脑浦肯野细胞(PC)特异性基因靶向研究了谷氨酸受体(GluR) δ2在成人脑中的作用。随着突触后GluRδ2蛋白的减少,突触前活动区逐渐缩小,突触后密度(PSD)增加,导致平行纤维- pc突触的突触前和突触后特化不匹配。此外,GluRδ2和PSD-93蛋白集中在不匹配突触的接触部分,而AMPA受体分布在接触和游离部分。当GluRδ2蛋白减少时,PC棘失去突触接触。因此,我们发现突触后GluRδ2是成人大脑中平行纤维- pc突触突触前活跃区和PSD组织的关键调节因子。
Precise topological matching of presynaptic and postsynaptic specializations is essential for efficient synaptic transmission. Furthermore, synaptic connections are subjected to rearrangements throughout life. Here we examined the role of glutamate receptor (GluR) δ2 in the adult brain by inducible and cerebellar Purkinje cell (PC)-specific gene targeting under the pure C57BL/6 genetic background. Concomitant with the decrease of postsynaptic GluRδ2 proteins, presynaptic active zones shrank progressively and postsynaptic density (PSD) expanded, resulting in mismatching between presynaptic and postsynaptic specializations at parallel fiber-PC synapses. Furthermore, GluRδ2 and PSD-93 proteins were concentrated at the contacted portion of mismatched synapses, whereas AMPA receptors were distributed in both the contacted and dissociated portions. When GluRδ2 proteins were diminished, PC spines lost their synaptic contacts. We thus identified postsynaptic GluRδ2 as a key regulator of the presynaptic active zone and PSD organization at parallel fiber-PC synapses in the adult brain.