A sequential two-step priming scheme reproduces diversity in synaptic strength and short-term plasticity.
A sequential two-step priming scheme reproduces diversity in synaptic strength and short-term plasticity.
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一个连续的两步启动方案再现多样性的突触强度和短期可塑性。
DOI：
10.1073/pnas.2207987119
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发表时间：
2022-08-23
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
中枢神经系统突触在强度和可塑性方面是多样的。传统上，短期可塑性的评估模型假定一个单一的池功能均匀的融合能力突触囊泡。许多观测结果不容易用这种简单的模型来解释。我们建立并实验验证了一个由两个顺序和可逆的释放机械组装步骤组成的突触囊泡引发方案。这种连续的两步启动方案忠实地再现了可塑性在mammatergic模型突触。所提出的启动和融合方案与测得的平均反应和实验观察到的突触之间的异质性是一致的。囊泡融合的概率被认为是相对均匀的突触，而启动平衡在休息的成熟与不成熟的囊泡启动状态差异很大。谷氨酸能突触显示可变的强度和不同的短期可塑性（STP），即使是一个给定的连接类型。使用非负张量因子分解和传统的状态建模，我们证明了一个动力学方案组成的两个顺序和可逆的步骤的释放机械组装和突触囊泡（SV）融合的最后一步重现STP和突触之间的多样性。在萼举行突触的分析传输表明，突触强度和STP的差异主要不是由可变的融合概率（灌注），但由停靠的突触囊泡配备了一个成熟的释放机械的分数所造成的。我们的模拟表明，传统的量子分析方法不一定报告灌注的SV与成熟的释放机制，但反映灌注和成熟和不成熟的启动状态之间的分布在休息。因此，该方法有望更好地机械解剖的SV对接，两步启动和融合的序列中的突触前蛋白质的作用。这表明了活动诱导的突触效能再分配的机制。
Central nervous system synapses are diverse in strength and plasticity. Short-term plasticity has traditionally been evaluated with models postulating a single pool of functionally homogeneous fusion-competent synaptic vesicles. Many observations are not easily explainable by such simple models. We established and experimentally validated a scheme of synaptic vesicle priming consisting of two sequential and reversible steps of release–machinery assembly. This sequential two-step priming scheme faithfully reproduced plasticity at a glutamatergic model synapse. The proposed priming and fusion scheme was consistent with the measured mean responses and with the experimentally observed heterogeneity between synapses. Vesicle fusion probability was found to be relatively uniform among synapses, while the priming equilibrium at rest of mature versus immature vesicle priming states differed greatly. 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 (pfusion) 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 pfusion of SVs with a mature release machinery but reflect both pfusion 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.
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影响因子：
16.2
作者：
Hua, Yunfeng;Woehler, Andrew;Klingauf, Juergen
通讯作者：
Klingauf, Juergen
影响因子：
16.6
作者：
He E;Wierda K;van Westen R;Broeke JH;Toonen RF;Cornelisse LN;Verhage M
通讯作者：
Verhage M
影响因子：
5.5
作者：
Debanne, D;Guerineau, NC;Thompson, SM
通讯作者：
Thompson, SM
影响因子：
5.5
作者：
Borst, JGG;Sakmann, B
通讯作者：
Sakmann, B
影响因子：
5.3
作者：
Chen, Zuxin;Das, Brati;Young, Samuel M., Jr.
通讯作者：
Young, Samuel M., Jr.