Distinct Nanoscale Calcium Channel and Synaptic Vesicle Topographies Contribute to the Diversity of Synaptic Function
Distinct Nanoscale Calcium Channel and Synaptic Vesicle Topographies Contribute to the Diversity of Synaptic Function
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DOI：
10.1101/421370
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发表时间：
2018-09
期刊：
影响因子：
16.2
通讯作者：
N. Rebola;M. Reva;Tekla Kirizs;Miklos Szoboszlay;G. Moneron;Z. Nusser;D. DiGregorio
中科院分区：
文献类型：
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作者：
N. Rebola;M. Reva;Tekla Kirizs;Miklos Szoboszlay;G. Moneron;Z. Nusser;D. DiGregorio
电压门控钙通道（VGCC）和突触囊泡（SV）的纳米级拓扑结构的安排决定了突触的强度和可塑性，但不同的空间分布是否支持突触功能的多样性是未知的。我们在两个小脑突触处进行了VGCC和活动区（AZ）蛋白Munc 13 -1的单端Ca 2+成像、Ca 2+螯合剂竞争、免疫金电子显微镜（EM）定位。出乎意料的是，我们发现弱突触的VGCC是强突触的3倍，而耦合距离是强突触的5倍。反应扩散模型可以用两种截然不同的纳米地形图案来解释功能和结构数据：强突触由与VGCC簇紧密耦合（~ 10 nm）的SV组成，而在弱突触处，VGCC被排除在邻近区域之外（~ 50 nm）对接囊泡。不同的VGCC-SV拓扑基序也赋予神经调节不同的敏感性。因此，VGCC-SV的安排是不规范的CNS突触和它们的多样性可能是功能异质性的基础。
The nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+ imaging, Ca2+ chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modelling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled (∼10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity (∼50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus VGCC-SV arrangements are not canonical across CNS synapses and their diversity could underlie functional heterogeneity.