Molecular mechanisms underlying the release dynamics of synaptic vesicles

采用大鼠小脑脑片全细胞膜片钳记录技术，观察了颗粒细胞（GC）到分子层中间神经元（INs）兴奋性突触传递过程中不同形式的成对脉冲易化（PPF）。短时间间隔（30-100 ms）配对脉冲激活GC上行轴突，不仅使INS记录的兴奋性突触后电流（EPSC）的峰值幅度（PPFamp）显著易化，而且使衰减时间常数（PPFdecay）显著易化。药理学测试、动力学分析和计算机模拟结果表明，不同类型的PPF的机制不同。PPFamp是由囊泡释放概率和释放囊泡多样性的双重增加引起的。另一方面，PPF衰减是由GC递质谷氨酸的突触外溢出和突触间汇集引起的。

Using the whole-cell patch clamp recording in rat cerebellar slices, we found different forms of paired-pulse facilitation (PPF) at the excitatory synaptic transmission from granule cells (GCs) to molecular-layer interneurons (INs). Paired-pulse activation of GC ascending axons at short intervals (30-100 ms) caused a significant facilitation not only in the peak amplitude (PPFamp) but also in the decay-time constant (PPFdecay) of the excitatory postsynaptic currents (EPSCs) recorded from INs. The results of pharmacological tests, kinetics analyses and computer simulations suggest that the mechanisms underlying the respective types of PPF were different. PPFamp was elicited by dual increase in the probability of the vesicular release and in the multiplicity of released vesicles. On the other hand, PPFdecay was caused by extrasynaptic spillover of the GC transmitter glutamate and following their intersynaptic pooling.