A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane. In this review, we consider mechanisms of trafficking of AMPA receptors to and from synapses that take place in the early trafficking stages, starting in the endoplasmic reticulum (ER) and continuing into the secretory pathway. We consider mechanisms of AMPA receptor assembly in the ER, highlighting the role of protein synthesis and the selective properties of specific AMPA receptor subunits, as well as regulation of ER exit, including the roles of chaperones and accessory proteins and the incorporation of AMPA receptors into COPII vesicles. We consider these processes in the context of the mechanism of mGluR LTD and discuss a compelling role for the dendritic ER membrane that is found proximal to synapses. The review illustrates the important, yet little studied, contribution of the early stages of AMPA receptor trafficking to synaptic plasticity.

大脑的基本属性是其响应自身活动而改变其功能的能力。这种自我修饰的能力在很大程度上取决于突触可塑性。现在已经认识到，对于兴奋性突触，突触可塑性的重要部分取决于对神经末梢释放的谷氨酸的突触后反应的变化。突触后反应的改变又取决于突触后膜中AMPA受体丰度的变化。在这篇综述中，我们考虑了AMPA受体往来于突触的运输机制，这些机制发生在早期的运输阶段，始于内质网（ER）并持续进入分泌途径。我们考虑了内质网中AMPA受体组装的机制，强调了蛋白质合成的作用和特定AMPA受体亚基的选择性特性，以及对ER出口的调节，包括分子伴侣和辅助蛋白的作用以及将AMPA受体掺入COPII囊泡中。我们在mGluR LTD机制的背景下考虑这些过程，并讨论了突触附近发现的树突状ER膜的引人注目的作用。审查表明，AMPA受体贩运的早期阶段对突触可塑性的重要但尚未研究。我们在mGluR LTD机制的背景下考虑这些过程，并讨论了突触附近发现的树突状ER膜的引人注目的作用。审查表明，AMPA受体贩运的早期阶段对突触可塑性的重要但尚未研究。我们在mGluR LTD机制的背景下考虑这些过程，并讨论了突触附近发现的树突状ER膜的引人注目的作用。审查表明，AMPA受体贩运的早期阶段对突触可塑性的重要但尚未研究。