Elevated synaptic vesicle release probability in synaptophysin/gyrin family quadruple knockouts

Synaptophysins 1 and 2 and synaptogyrins 1 and 3 constitute a major family of synaptic vesicle membrane proteins. Unlike other widely expressed synaptic vesicle proteins such as vSNAREs and synaptotagmins, the primary function has not been resolved. Here, we report robust elevation in the probability of release of readily releasable vesicles with both high and low release probabilities at a variety of synapse types from knockout mice missing all four family members. Neither the number of readily releasable vesicles, nor the timing of recruitment to the readily releasable pool was affected. The results suggest that family members serve as negative regulators of neurotransmission, acting directly at the level of exocytosis to dampen connection strength selectively when presynaptic action potentials fire at low frequency. The widespread expression suggests that chemical synapses may play a frequency filtering role in biological computation that is more elemental than presently envisioned.突触素（Synaptophysin）1、2与突触旋蛋白（synaptogyrin）1、3共同构成了突触囊泡膜蛋白的一个主要家族。与v-SNARE蛋白、突触结合蛋白（synaptotagmin）等广泛表达的突触囊泡蛋白不同，该家族成员的核心功能迄今尚未阐明。本研究针对缺失全部四个家族成员的基因敲除小鼠开展实验，在多种突触类型中观察到，高释放概率与低释放概率的易释放囊泡的释放概率均出现显著升高。易释放囊泡的数量以及其向易释放池募集的时间进程均未受影响。研究结果表明，该家族成员作为神经传递的负调控因子，直接作用于胞吐过程，在突触前动作电位以低频发放时选择性地抑制突触连接强度。该家族的广泛表达提示，化学突触在生物计算中可能承担着比当前认知更为基础的频率过滤功能。