Emeritus Laboratory of Membrane Biophysics, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, 37075 Göttingen, Germany.
Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2207987119. doi: 10.1073/pnas.2207987119. Epub 2022 Aug 15.
Glutamatergic synapses display variable strength and diverse short-term plasticity (STP), even for a given type of connection. Using nonnegative tensor factorization and conventional state modeling, we demonstrate that a kinetic scheme consisting of two sequential and reversible steps of release-machinery assembly and a final step of synaptic vesicle (SV) fusion reproduces STP and its diversity among synapses. Analyzing transmission at the calyx of Held synapses reveals that differences in synaptic strength and STP are not primarily caused by variable fusion probability () but are determined by the fraction of docked synaptic vesicles equipped with a mature release machinery. Our simulations show that traditional quantal analysis methods do not necessarily report of SVs with a mature release machinery but reflect both and the distribution between mature and immature priming states at rest. Thus, the approach holds promise for a better mechanistic dissection of the roles of presynaptic proteins in the sequence of SV docking, two-step priming, and fusion. It suggests a mechanism for activity-induced redistribution of synaptic efficacy.
谷氨酸能突触表现出可变的强度和多样的短期可塑性（STP），即使对于给定类型的连接也是如此。使用非负张量分解和传统的状态建模，我们证明了由两个连续的、可逆的释放机制组装步骤和一个最终的突触小泡（SV）融合步骤组成的动力学方案可以再现 STP 及其在突触间的多样性。在 Held 神经突触的分析表明，突触强度和 STP 的差异不是由可变融合概率（）引起的，而是由配备成熟释放机制的停靠突触小泡的分数决定的。我们的模拟表明，传统的量子分析方法不一定报告具有成熟释放机制的 SV 的，但反映了成熟和不成熟引发状态在静止时的分布。因此，这种方法有望更好地从机制上剖析突触前蛋白在 SV 停靠、两步引发和融合顺序中的作用。它为活性诱导的突触效能重新分布提供了一种机制。
