Department of Biological Sciences, Konkuk University, Seoul, South Korea.
J Neurochem. 2013 Jul;126(2):146-54. doi: 10.1111/jnc.12245. Epub 2013 Apr 23.
Central synapses operate neurotransmission in several modes: synchronous/fast neurotransmission (neurotransmitters release is tightly coupled to action potentials and fast), asynchronous neurotransmission (neurotransmitter release is slower and longer lasting), and spontaneous neurotransmission (where small amounts of neurotransmitter are released without being evoked by an action potential). A substantial body of evidence from the past two decades suggests that seemingly identical synaptic vesicles possess distinct propensities to fuse, thus selectively serving different modes of neurotransmission. In efforts to better understand the mechanism(s) underlying the different modes of synaptic transmission, many research groups found that synaptic vesicles used in different modes of neurotransmission differ by a number of synaptic proteins. Synchronous transmission with higher temporal fidelity to stimulation seems to require synaptotagmin 1 and complexin for its Ca²⁺ sensitivity, RIM proteins for closer location of synaptic vesicles (SV) to the voltage operated calcium channels (VGCC), and dynamin for SV retrieval. Asynchronous release does not seem to require functional synaptotagmin 1 as a calcium sensor or complexins, but the activity of dynamin is indispensible for its maintenance. On the other hand, the control of spontaneous neurotransmission remains less clear as deleting a number of essential synaptic proteins does not abolish this type of synaptic vesicle fusion. VGCC distance from the SV seems to have little control on spontaneous transmission, while there is an involvement of functional synaptic proteins including synaptotagmins and complexin. Recently, presynaptic deficits have been proposed to contribute to a number of pathological conditions including cognitive and mental disorders. In this review, we evaluate recent advances in understanding the regulatory mechanisms of synaptic vesicle dynamics and in understanding how different molecular substrates maintain selective modes of neurotransmission. We also highlight the implications of these studies in understanding pathological conditions.
同步/快速神经传递（神经递质的释放与动作电位紧密偶联且迅速）、异步神经传递（神经递质的释放较慢且持续时间较长）和自发性神经传递（少量神经递质在没有动作电位触发的情况下释放）。过去二十年的大量证据表明，看似相同的突触小泡具有不同的融合倾向，从而选择性地服务于不同的神经传递模式。为了更好地理解不同神经传递模式的机制，许多研究小组发现，用于不同神经传递模式的突触小泡在许多突触蛋白上存在差异。具有更高时间精度的同步传递似乎需要突触融合蛋白 1 和复合蛋白来提高 Ca²⁺敏感性、RIM 蛋白使突触小泡 (SV) 更接近电压门控钙通道 (VGCC)、以及动力蛋白用于 SV 回收。异步释放似乎不需要功能性突触融合蛋白 1 作为钙传感器或复合蛋白，但动力蛋白的活性对于其维持是不可或缺的。另一方面，自发性神经传递的控制仍然不太清楚，因为删除许多必需的突触蛋白并不能消除这种类型的突触小泡融合。SVGCC 与 SV 的距离似乎对自发性传递的控制作用不大，而功能性突触蛋白包括突触融合蛋白和复合蛋白的参与则起着一定作用。最近，人们提出突触前缺陷可能导致包括认知和精神障碍在内的许多病理状况。在这篇综述中，我们评估了理解突触小泡动力学调节机制和理解不同分子底物如何维持选择性神经传递模式的最新进展。我们还强调了这些研究在理解病理状况方面的意义。
