Mameli Manuel, Balland Bénédicte, Luján Rafael, Lüscher Christian
Department of Basic Neuroscience, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland.
Science. 2007 Jul 27;317(5837):530-3. doi: 10.1126/science.1142365.
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.
代谢型谷氨酸受体（mGluRs）的激活会在大脑的许多突触处引发长时程抑制（mGluR-LTD）。mGluR-LTD的诱导过程已得到充分表征，但其表达背后的机制仍 largely难以捉摸。腹侧被盖区（VTA）中的mGluR-LTD能有效逆转可卡因诱导的多巴胺神经元兴奋性输入增强。我们发现，mGluR-LTD是通过缺乏GluR2的AMPA受体与单通道电导较低的含GluR2受体进行交换来表达的。GluR2的突触插入依赖于通过GluR2的快速信使核糖核酸翻译进行的从头蛋白质合成。因此，VTA中GluR2的调节合成是逆转可卡因诱导的突触可塑性所必需的。
