Tokuoka Hirofumi, Goda Yukiko
Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14656-61. doi: 10.1073/pnas.0805705105. Epub 2008 Sep 15.
The strength of an excitatory synapse depends on both the presynaptic release probability (p(r)) and the abundance of functional postsynaptic AMPA receptors. How these parameters are related or balanced at a single synapse remains unknown. By taking advantage of live fluorescence imaging in cultured hippocampal neurons where individual synapses are readily resolved, we estimate p(r) by labeling presynaptic vesicles with a styryl dye, FM1-43, while concurrently measuring postsynaptic AMPA receptor abundance at the same synapse by immunolabeling surface GluR2. We find no appreciable correlation between p(r) and the level of surface synaptic GluR2 under basal condition, and blocking basal neural activity has no effect on the observed lack of correlation. However, elevating network activity drives their correlation, which accompanies a decrease in mean GluR2 level. These findings provide the direct evidence that the coordination of pre- and postsynaptic parameters of synaptic strength is not intrinsically fixed but that the balance is tuned by synaptic use at individual synapses.
兴奋性突触的强度取决于突触前释放概率（p(r)）和功能性突触后AMPA受体的丰度。在单个突触处，这些参数如何关联或平衡仍是未知的。通过利用培养的海马神经元中的实时荧光成像技术（其中单个突触易于分辨），我们用一种苯乙烯基染料FM1-43标记突触前囊泡来估计p(r)，同时通过免疫标记表面GluR2来测量同一突触处的突触后AMPA受体丰度。我们发现在基础条件下，p(r)与表面突触GluR2水平之间没有明显的相关性，并且阻断基础神经活动对观察到的缺乏相关性没有影响。然而，提高网络活动会促使它们产生相关性，这伴随着平均GluR2水平的降低。这些发现提供了直接证据，表明突触强度的突触前和突触后参数的协调并非内在固定不变，而是这种平衡在单个突触处由突触使用情况进行调节。
