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摘要 : 一直以来,人们推测有效的神经传输需要突触前囊泡释放点和突触后受体的精准对应,但受光学显微镜的物理特性限制,一直未能进行直接观察。

 一直以来,人们推测有效的神经传输需要突触前囊泡释放点和突触后受体的精准对应,但受光学显微镜的物理特性限制,一直未能进行直接观察。Thomas Blanpied及同事使用超分辨率显微镜克服了衍射障碍,揭示了由动作电位触发的单个突触囊泡融合是被局限于突触前蛋白纳米团簇的。这些纳米团簇与集中的突触后受体及其支架蛋白紧密对应,所产生的分子“纳米柱”在NMDA受体依赖型可塑性期间发生重组。作者提出,它们可能有助于维持和调节突触效率。


A trans-synaptic nanocolumn aligns neurotransmitter release to receptors


Synaptic transmission is maintained by a delicate, sub-synaptic molecular architecture, and even mild alterations in synapse structure drive functional changes during experience-dependent plasticity and pathological disorders1, 2. Key to this architecture is how the distribution of presynaptic vesicle fusion sites corresponds to the position of receptors in the postsynaptic density. However, while it has long been recognized that this spatial relationship modulates synaptic strength3, it has not been precisely described, owing in part to the limited resolution of light microscopy. Using localization microscopy, here we show that key proteins mediating vesicle priming and fusion are mutually co-enriched within nanometre-scale subregions of the presynaptic active zone. Through development of a new method to map vesicle fusion positions within single synapses in cultured rat hippocampal neurons, we find that action-potential-evoked fusion is guided by this protein gradient and occurs preferentially in confined areas with higher local density of Rab3-interacting molecule (RIM) within the active zones. These presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins4, 5, 6, suggesting the existence of a trans-synaptic molecular ‘nanocolumn’. Thus, we propose that the nanoarchitecture of the active zone directs action-potential-evoked vesicle fusion to occur preferentially at sites directly opposing postsynaptic receptor–scaffold ensembles. Remarkably, NMDA receptor activation triggered distinct phases of plasticity in which postsynaptic reorganization was followed by trans-synaptic nanoscale realignment. This architecture suggests a simple organizational principle of central nervous system synapses to maintain and modulate synaptic efficiency.

来源: Nature 浏览次数:0


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