A use-dependent increase in release sites drives facilitation at calretinin-deficient cerebellar parallel-fiber synapses.

A use-dependent increase in release sites drives facilitation at calretinin-deficient cerebellar parallel-fiber synapses.
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DOI:
10.3389/fncel.2015.00027
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发表时间:
2015
影响因子:
5.3
通讯作者:
Schmidt H
Schmidt H
中科院分区:
医学2区
文献类型:
--
作者:
Brachtendorf S;Eilers J;Schmidt H

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内源性钙结合蛋白通过缓冲突触前钙信号影响突触递质释放和短时程可塑性。在小脑皮层的平行纤维(PF)-浦肯野神经元(PN)突触中,PF末端的主要缓冲区钙视网膜蛋白(CR)的丢失导致突触前Ca 2+瞬变增加,初始囊泡释放概率(pr)几乎增加了一倍。然而,令人惊讶的是,据报道,从PF突触的CR损失不会改变成对脉冲易化(PPF),而它会影响突触前Ca 2+信号以及pr。在这里,我们解决了这个令人困惑的观察,通过分析频率和Ca 2+依赖性的PPF在单一的PF到PN突触的野生型(WT)和CR缺陷(CR-/-)小鼠使用配对记录和计算机模拟。我们的分析显示,CR-/-的PPF确实小于WT,但在一定程度上,这表明囊泡的快速补充和额外释放位点的募集主导了第二反应的突触功效。这些Ca 2+驱动的过程在没有CR的情况下更有效地操作,从而解释了突变体中稳健的PPF的保存。
Endogenous Ca2+-binding proteins affect synaptic transmitter release and short-term plasticity (STP) by buffering presynaptic Ca2+ signals. At parallel-fiber (PF)-to-Purkinje neuron (PN) synapses in the cerebellar cortex loss of calretinin (CR), the major buffer at PF terminals, results in increased presynaptic Ca2+ transients and an almost doubling of the initial vesicular releases probability (pr). Surprisingly, however, it has been reported that loss of CR from PF synapses does not alter paired-pulse facilitation (PPF), while it affects presynaptic Ca2+ signals as well as pr. Here, we addressed this puzzling observation by analyzing the frequency- and Ca2+-dependence of PPF at unitary PF-to-PN synapses of wild-type (WT) and CR-deficient (CR−/−) mice using paired recordings and computer simulations. Our analysis revealed that PPF in CR−/− is indeed smaller than in the WT, to a degree, however, that indicates that rapid vesicle replenishment and recruitment of additional release sites dominate the synaptic efficacy of the second response. These Ca2+-driven processes operate more effectively in the absence of CR, thereby, explaining the preservation of robust PPF in the mutants.
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