RG Functional Neurobiology, Institute of Developmental Biology and Neurobiology, Johannes-Gutenberg-University Mainz, Hanns-Dieter-Hüsch-Weg 15, D-55128 Mainz, Germany.
Data Modeling and Computational Biology Group, Institute for Biology, École Normale Supérieure and Université Paris Sciences et Lettres (PSL Research University), Paris, France; Department of Applied Mathematics and Theoretical Physics (DAMPT) and Churchill College, University of Cambridge, Cambridge CB3 0DS, UK.
Trends Neurosci. 2020 Mar;43(3):182-196. doi: 10.1016/j.tins.2020.01.005. Epub 2020 Feb 13.
Synaptic transmission and plasticity are shaped by the dynamic reorganization of signaling molecules within pre- and postsynaptic compartments. The nanoscale organization of key effector molecules has been revealed by single-particle trajectory (SPT) methods. Interestingly, this nanoscale organization is highly heterogeneous. For example, presynaptic voltage-gated calcium channels (VGCCs) and postsynaptic ligand-gated ion channels such as AMPA receptors (AMPARs) are organized into so-called nanodomains where individual molecules are only transiently trapped. These pre- and postsynaptic nanodomains are characterized by a high density of molecules but differ in their molecular organization and stability within the synaptic membrane. We review the main properties of these nanodomains, as well as the methods developed to extract parameters from SPT experiments. We discuss how such molecular dynamics influences synaptic transmission. The nanoscale organization of active synapses opens new insights into the dynamics and turnover of molecules as well as casting light on their contributions to signal transfer between individual neurons.
突触传递和可塑性是通过信号分子在突触前和突触后隔室中的动态重排来塑造的。关键效应分子的纳米级组织已通过单粒子轨迹 (SPT) 方法揭示。有趣的是,这种纳米级组织具有高度的异质性。例如,突触前电压门控钙通道 (VGCC) 和突触后配体门控离子通道,如 AMPA 受体 (AMPAR),组织成所谓的纳米域,其中单个分子仅短暂被困。这些突触前和突触后纳米域的特点是分子密度高,但在突触膜内的分子组织和稳定性上有所不同。我们回顾了这些纳米域的主要特性,以及从 SPT 实验中提取参数的方法。我们讨论了这种分子动力学如何影响突触传递。活性突触的纳米级组织为分子的动力学和周转提供了新的见解,并阐明了它们对单个神经元之间信号传递的贡献。