Contribution of Postsynaptic GluD2 to Presynaptic R-type Ca2+ Channel Function, Glutamate Release and Long-term Potentiation at Parallel Fiber to Purkinje Cell Synapses
Contribution of Postsynaptic GluD2 to Presynaptic R-type Ca2+ Channel Function, Glutamate Release and Long-term Potentiation at Parallel Fiber to Purkinje Cell Synapses
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DOI：
10.1007/s12311-013-0474-y
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发表时间：
2013-04
期刊：
影响因子：
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通讯作者：
Manami Yamashita;Shin-ya Kawaguchi;T. Hirano
中科院分区：
文献类型：
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作者：
Manami Yamashita;Shin-ya Kawaguchi;T. Hirano
谷氨酸受体样分子δ 2（GluD 2）选择性表达于小脑中平行纤维-浦肯野细胞（PF-PC）突触的突触后膜上。GluD 2不仅在突触后长时程抑制中起关键作用，而且通过与neurexin的跨突触相互作用在诱导突触前分化中也起关键作用。然而，GluD 2如何影响突触前功能仍不清楚。在这里，突触后GluD 2的缺失对突触前特性的影响进行了研究，集中在成对脉冲比（PPR）的两个连续的EPSC振幅，这是较大的GluD 2基因敲除小鼠。即使谷氨酸结合到突触后受体的饱和度被抑制，PPR差异仍然存在，证实了基因型之间的突触前差异。然后，我们探讨了突触前电压门控钙通道（VGCC）的可能性，在GluD 2基因敲除小鼠的影响。特异性VGCC选择性阻断剂的应用表明，在突变小鼠中，R型而不是P/Q型或N型VGCC受到影响。此外，突触前长时程增强（LTP）在PF-PC突触，这需要R型VGCC，受损GluD 2基因敲除小鼠。这些结果表明，GluD 2缺失损害突触前R型VGCC，导致突触囊泡释放减少，也在突触前LTP在PF-PC突触的损害。
Glutamate-receptor-like molecule delta2 (GluD2) is selectively expressed on the postsynaptic membranes at parallel fiber to Purkinje cell (PF-PC) synapses in the cerebellum. GluD2 plays critical roles not only in postsynaptic long-term depression but also in the induction of presynaptic differentiation through trans-synaptic interaction with neurexin. However, how GluD2 influences the presynaptic function remains unknown. Here, effects of the deletion of postsynaptic GluD2 on the presynaptic properties were studied focusing on the paired pulse ratio (PPR) of two consecutive EPSC amplitudes, which was larger in GluD2 knockout mice. The PPR difference remained even if saturation of glutamate binding to postsynaptic receptors was suppressed, confirming the presynaptic difference between the genotypes. We then explored the possibility that presynaptic voltage-gated Ca2+channels (VGCCs) are affected in GluD2 knockout mice. Application of selective blockers for specific VGCCs indicated that R-type but not P/Q- or N-type VGCC, was affected in the mutant mice. Furthermore, presynaptic long-term potentiation (LTP) at PF-PC synapses, which requires R-type VGCC, was impaired in GluD2 knockout mice. These results suggest that GluD2 deletion impairs presynaptic R-type VGCC, resulting in decreased release of synaptic vesicles, and also in the impairment of presynaptic LTP at PF-PC synapses.