The δ2 'ionotropic' glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity
The δ2 'ionotropic' glutamate receptor functions as a non-ionotropic receptor to control cerebellar synaptic plasticity
复制标题
DOI：
10.1113/jphysiol.2007.141291
复制
发表时间：
2007-10-01
影响因子：
5.5
通讯作者：
Yuzaki, Michisuke
中科院分区：
文献类型：
--
作者：
Kakegawa, Wataru;Kohda, Kazuhisa;Yuzaki, Michisuke
δ 2谷氨酸受体（GluR δ 2）属于离子型谷氨酸受体（iGluR）家族，在诱导小脑长时程抑制（LTD）中起着至关重要的作用，LTD是运动学习的突触可塑性形式。然而，GluR δ 2调节小脑LTD的机制仍然难以捉摸。因为在lurcher小鼠中发生的突变引起连续的GluR δ 2通道活性，该活性可以被1-萘基乙酰精胺（NASP）（一种Ca 2+渗透性iGluR的通道阻断剂）消除，所以GluR δ 2被认为起离子通道的作用。在这里，我们引入了一个突变体GluR δ 2转基因，其中假定的通道孔被破坏，到GluR δ 2-空浦肯野细胞使用病毒载体。令人惊讶的是，与野生型GluR δ 2转基因的作用相似，突变型GluR δ 2完全挽救了GluR δ 2缺失小鼠中废除的LTD。此外，NASP没有阻断LTD诱导野生型小脑切片。这些结果表明，GluR δ 2，iGluR家族的成员，不作为一个通道，在调节LTD诱导。
The delta 2 glutamate receptor (GluR delta 2) belongs to the ionotropic glutamate receptor (iGluR) family and plays a crucial role in the induction of cerebellar long-term depression (LTD), a form of synaptic plasticity underlying motor learning. Nevertheless, the mechanisms by which GluR delta 2 regulates cerebellar LTD have remained elusive. Because a mutation occurring in lurcher mice causes continuous GluR delta 2 channel activity that can be abolished by 1-naphtylacetylspermine (NASP), a channel blocker for Ca2+-permeable iGluRs, GluR delta 2 is thought to function as an ion channel. Here, we introduced a mutant GluR delta 2 transgene, in which the putative channel pore was disrupted, into GluR delta 2-null Purkinje cells using a virus vector. Surprisingly and similar to the effect of the wild-type GluR delta 2 transgene, the mutant GluR delta 2 completely rescued the abrogated LTD in GluR delta 2-null mice. Furthermore, NASP did not block LTD induction in wild-type cerebellar slices. These results indicate that GluR delta 2, a member of the iGluR family, does not serve as a channel in the regulation of LTD induction.