Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area
Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area
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DOI：
10.1126/science.1142365
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发表时间：
2007-07-27
期刊：
影响因子：
56.9
通讯作者：
Luescher, Christian
中科院分区：
文献类型：
--
作者：
Mameli, Manuel;Balland, Benedicte;Luescher, Christian
代谢型谷氨酸受体（mGluR）的激活导致脑的许多突触处的长期抑制（mGluR-LTD）。mGluR-LTD的诱导被很好地表征，而其表达的机制在很大程度上仍然难以捉摸。腹侧被盖区（VTA）中的mGluR-LTD有效地逆转可卡因诱导的对多巴胺神经元的兴奋性输入的加强。我们表明，mGluR-LTD表达的交换GluR 2缺乏AMPA受体含GluR 2受体具有较低的单通道电导。GluR 2的突触插入依赖于通过GluR 2的快速信使RNA翻译的从头蛋白质合成。因此，需要调节腹侧被盖区中GluR 2的合成来逆转可卡因诱导的突触可塑性。
The activation of metabotropic glutamate receptors (mGluRs) leads to long-term depression (mGluR-LTD) at many synapses of the brain. The induction of mGluR-LTD is well characterized, whereas the mechanisms underlying its expression remain largely elusive. mGluR-LTD in the ventral tegmental area (VTA) efficiently reverses cocaine-induced strengthening of excitatory inputs onto dopamine neurons. We show that mGluR-LTD is expressed by an exchange of GluR2-lacking AMPA receptors for GluR2-containing receptors with a lower single-channel conductance. The synaptic insertion of GluR2 depends on de novo protein synthesis via rapid messenger RNA translation of GluR2. Regulated synthesis of GluR2 in the VTA is therefore required to reverse cocaine-induced synaptic plasticity.