Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity. Intriguingly, these receptors are differentially distributed with respect to the presynaptic release site. While iGluRs are enriched in the core of the synapse directly opposing the release site, mGluRs reside preferentially at the border of the synapse. As such, to understand the differential contribution of these receptors to synaptic transmission, it is important to not only consider their signaling properties, but also the mechanisms that control the spatial segregation of these receptor types within synapses. In this review, we will focus on the mechanisms that control the organization of glutamate receptors at the postsynaptic membrane with respect to the release site, and discuss how this organization could regulate synapse physiology.

谷氨酸受体是大脑中最丰富的兴奋性神经递质受体，负责介导神经元网络中的绝大多数兴奋性传递。 AMPA 和 NMDA 型离子型谷氨酸受体 (iGluR) 是配体门控离子通道，介导快速突触反应，而代谢型谷氨酸受体 (mGluR) 与下游信号级联耦合，其作用时间尺度要慢得多。这些功能不同的受体亚型在各个突触处共同表达，从而可以对突触后兴奋性和可塑性进行精确的时间调节。有趣的是，这些受体在突触前释放位点的分布存在差异。虽然 iGluR 富集在与释放位点直接相对的突触核心，但 mGluR 优先存在于突触边缘。因此，为了了解这些受体对突触传递的不同贡献，重要的是不仅要考虑它们的信号传导特性，还要考虑控制突触内这些受体类型的空间分离的机制。在这篇综述中，我们将重点关注控制突触后膜谷氨酸受体释放位点组织的机制，并讨论该组织如何调节突触生理学。