Department of Neuro- and Sensory Physiology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
Max-Planck-Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen, Germany.
Cell Rep. 2021 Mar 16;34(11):108841. doi: 10.1016/j.celrep.2021.108841.
Synaptic transmission relies on the continual exocytosis and recycling of synaptic vesicles. Aged vesicle proteins are prevented from recycling and are eventually degraded. This implies that active synapses would lose vesicles and vesicle-associated proteins over time, unless the supply correlates to activity, to balance the losses. To test this hypothesis, we first model the quantitative relation between presynaptic spike rate and vesicle turnover. The model predicts that the vesicle supply needs to increase with the spike rate. To follow up this prediction, we measure protein turnover in individual synapses of cultured hippocampal neurons by combining nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence microscopy. We find that turnover correlates with activity at the single-synapse level, but not with other parameters such as the abundance of synaptic vesicles or postsynaptic density proteins. We therefore suggest that the supply of newly synthesized proteins to synapses is closely connected to synaptic activity.
突触传递依赖于突触囊泡的持续胞吐和再循环。老化的囊泡蛋白无法再循环，最终被降解。这意味着活跃的突触会随着时间的推移失去囊泡和囊泡相关蛋白，除非供应与活动相关，以平衡损失。为了验证这一假说，我们首先建立了突触前尖峰率和囊泡周转率之间的定量关系模型。该模型预测，囊泡供应需要随尖峰率增加。为了验证这一预测，我们通过结合纳米二次离子质谱（nanoSIMS）和荧光显微镜，测量培养的海马神经元中单个突触的蛋白质周转率。我们发现，周转率与单个突触水平的活动相关，但与囊泡或突触后密度蛋白的丰度等其他参数无关。因此，我们认为新合成蛋白质向突触的供应与突触活动密切相关。
