The weight of synaptic connections, which is controlled not only postsynaptically but also presynaptically, is a key determinant in neuronal network dynamics. The mechanisms controlling synaptic weight, especially on the presynaptic side, remain elusive. Using single-synapse imaging of the neurotransmitter glutamate combined with super-resolution imaging of presynaptic proteins, we identify a presynaptic mechanism for setting weight in central glutamatergic synapses. In the presynaptic terminal, Munc13-1 molecules form multiple and discrete supramolecular self-assemblies that serve as independent vesicular release sites by recruiting syntaxin-1, a soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) protein essential for synaptic vesicle exocytosis. The multiplicity of these Munc13-1 assemblies affords multiple stable states conferring presynaptic weight, potentially encoding several bits of information at individual synapses. Supramolecular assembling enables a stable synaptic weight, which confers robustness of synaptic computation on neuronal circuits and may be a general mechanism by which biological processes operate despite the presence of molecular noise.

中文翻译：

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由Munc13-1超分子组装设定的突触重量。

不仅通过突触后而且通过突触前控制的突触连接的权重是神经元网络动力学中的关键决定因素。控制突触重量，特别是在突触前侧的机制仍然难以捉摸。使用神经递质谷氨酸的单突触成像结合突触前蛋白的超分辨率成像，我们确定了在中央谷氨酸能突触中设定权重的突触前机制。在突触前末端，Munc13-1分子形成多个离散的超分子自组装体，通过募集syntaxin-1（一种对突触囊泡胞吐作用必不可少的可溶性N-乙基马来酰亚胺敏感因子附着受体（SNARE）蛋白）充当独立的囊泡释放位点。 。这些Munc13-1组件的多样性提供了赋予突触前权重的多个稳定状态，可能在各个突触处编码几位信息。超分子组装使得突触重量稳定，这赋予了神经元回路突触计算的鲁棒性，并且可能是尽管存在分子噪声但生物学过程仍在运行的通用机制。