UCL Institute of Neurology, University College London, United Kingdom.
PLoS Biol. 2012;10(9):e1001396. doi: 10.1371/journal.pbio.1001396. Epub 2012 Sep 25.
The efficacy of action potential evoked neurotransmitter release varies widely even among synapses supplied by the same axon, and the number of release-ready vesicles at each synapse is a major determinant of this heterogeneity. Here we identify a second, equally important, mechanism for release heterogeneity at small hippocampal synapses, the inter-synaptic variation of the exocytosis probability of release-ready vesicles. Using concurrent measurements of vesicular pool sizes, vesicular exocytosis rates, and presynaptic Ca²⁺ dynamics, in the same small hippocampal boutons, we show that the average fusion probability of release-ready vesicles varies among synapses supplied by the same axon with the size of the spike-evoked Ca²⁺ concentration transient. We further show that synapses with a high vesicular release probability exhibit a lower Ca²⁺ cooperativity, arguing that this is a direct consequence of increased Ca²⁺ influx at the active zone. We conclude that variability of neurotransmitter release under basal conditions at small central synapses is accounted for not only by the number of release-ready vesicles, but also by their fusion probabilities, which are set independently of bouton size by variable spike-evoked presynaptic Ca²⁺ influx.
动作电位诱发的神经递质释放的功效在即使是由同一轴突供应的突触中也有很大差异，而每个突触中准备释放的囊泡数量是这种异质性的主要决定因素。在这里，我们在小海马突触中发现了第二个同样重要的释放异质性机制，即准备释放的囊泡的胞吐概率的突触间变化。我们使用囊泡池大小、囊泡胞吐率和突触前 Ca²⁺动力学的同时测量，在同一小海马末梢中，表明来自同一轴突供应的突触之间的准备释放的囊泡的平均融合概率随尖峰诱发的 Ca²⁺浓度瞬变的大小而变化。我们进一步表明，具有高囊泡释放概率的突触表现出较低的 Ca²⁺协同性，这表明这是由于在活性区增加了 Ca²⁺内流的直接结果。我们的结论是，在小中枢突触的基础条件下，神经递质释放的可变性不仅由准备释放的囊泡数量决定，还由其融合概率决定，这些概率由刺激诱发的突触前 Ca²⁺内流的变化独立设定。
