孙坚原，中国科学院深圳先进技术研究院脑所研究员，中国科学院大学岗位教授，国际杂志《synapse》和《Membrane Traffic》编委。从事突触传递和神经信息处理的研究，聚焦神经递质量子化释放的机制和短时程突触可塑性。
The recycling vesicle pool, with proper kinetics, ensures sustained synaptic transmission. However, the kinetic structure of recycling vesicle pool has never been quantitatively analyzed before, and most studies were performed at room temperature and under resting conditions. With the combination of presynaptic capacitance measurement and postsynaptic EPSC recording on calyx of Held synapses at physiological temperature, we studied vesicle recycling under sustained presynaptic stimulation. The kinetics of vesicle reuse was revealed by impeding transmitter refilling with folimycin. We found that more than 90% of vesicles in nerve terminals are involved in recycling but they were not homogeneously competent for immediate reuse. A significant surface pool of vesicles, assayed as an increased capacitance, was detected with different levels corresponding to different stimulation intensities. We kinetically dissected the recycling vesicle pool as sequentially connected sub-pools (readily priming pool, readily releasable pool, surface pool and post-endocytic pool) and depicted the complete kinetic structure. The sizes and transition rates among these sub-pools were dynamically regulated by neuronal activity, in order to ensure efficient synaptic transmission. Furthermore, the dissected kinetic structure of recycling vesicle pools was found to function as a low pass filter to “forget” the short history of synaptic activity and thus reduce the impact of previous synaptic activity on the ongoing synaptic transmission. Our work provided a new insight into the function of vesicle recycling that the machinery of vesicle recycling functions not only a vesicle provider but also a stabilizer of synaptic transmission to ensure short term plasticity based neuronal signaling.
