Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands.
Department of Functional Genomics, Faculty of Exact Science, Center for Neurogenomics and Cognitive Research, VU University Amsterdam and VU Medical Center, Amsterdam, The Netherlands.
EMBO J. 2018 Oct 15;37(20). doi: 10.15252/embj.201899672. Epub 2018 Sep 5.
Neuropeptides are essential signaling molecules transported and secreted by dense-core vesicles (DCVs), but the number of DCVs available for secretion, their subcellular distribution, and release probability are unknown. Here, we quantified DCV pool sizes in three types of mammalian CNS neurons and Super-resolution and electron microscopy reveal a total pool of 1,400-18,000 DCVs, correlating with neurite length. Excitatory hippocampal and inhibitory striatal neurons have a similar DCV density, and thalamo-cortical axons have a slightly higher density. Synapses contain on average two to three DCVs, at the periphery of synaptic vesicle clusters. DCVs distribute equally in axons and dendrites, but the vast majority (80%) of DCV fusion events occur at axons. The release probability of DCVs is 1-6%, depending on the stimulation. Thus, mammalian CNS neurons contain a large pool of DCVs of which only a small fraction can fuse, preferentially at axons.
神经肽是由致密核心囊泡 (DCV) 运输和分泌的必需信号分子,但可用于分泌的 DCV 数量、它们的亚细胞分布和释放概率尚不清楚。在这里,我们定量了三种类型的哺乳动物中枢神经系统神经元中的 DCV 池大小,超分辨率和电子显微镜显示总共有 1400-18000 个 DCV,与神经突长度相关。兴奋性海马和抑制性纹状体神经元具有相似的 DCV 密度,而丘脑皮质轴突的密度略高。突触平均含有两个到三个 DCV,位于突触小泡簇的外围。DCV 在轴突和树突中均匀分布,但绝大多数(80%)的 DCV 融合事件发生在轴突上。DCV 的释放概率为 1-6%,具体取决于刺激。因此,哺乳动物中枢神经系统神经元中含有大量的 DCV,其中只有一小部分可以融合,优先在轴突上融合。