Paired-pulse facilitation at recurrent Purkinje neuron synapses is independent of calbindin and parvalbumin during high-frequency activation
Paired-pulse facilitation at recurrent Purkinje neuron synapses is independent of calbindin and parvalbumin during high-frequency activation
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DOI：
10.1113/jphysiol.2013.254128
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发表时间：
2013-07-01
影响因子：
5.5
通讯作者：
Schmidt, Hartmut
中科院分区：
文献类型：
--
作者：
Bornschein, Grit;Arendt, Oliver;Schmidt, Hartmut
配对脉冲促进（PPF）是一种动态增强的递质释放，在中枢神经系统信息处理中被认为是至关重要的。PPF的机制仍有争议，可能在突触之间有所不同。内源性Ca2+缓冲物如细小蛋白（PV）和钙结合蛋白- d28k （CB）被认为是PPF的重要调节剂，其中PV是一种抗促进缓冲物，而CB的饱和可以促进PPF。我们分析了皮层内，循环浦肯野神经元（PN）到PN突触的递质释放和PPF，这些突触在高频激活（200 Hz）时显示PPF，并强烈表达PV和CB。我们量化了野生型（WT）、CB和PV缺陷小鼠的突触前Ca2+动力学和定量释放参数。缺乏CB导致突触前Ca2+的体积平均振幅增加和释放概率增加，而PV的损失对这些参数没有显著影响。出乎意料的是，没有一种缓冲液显著影响PPF，这表明CB饱和度和剩余游离Ca2+ ([Ca2+](res))都不是PPF的主要决定因素。在实验约束下，使用Ca2+依赖释放的数值模拟来估计[Ca2+](res)， CB， PV, calmodulin (CaM)，固定缓冲部分和Ca2+在两个动作电位（活性Ca2+'）中的第一个动作电位后对PPF的释放传感器的贡献。该分析表明，PN-PN突触的PPF不是由缓冲液饱和或[Ca2+]（res）引起的，而是由释放传感器缓慢的Ca2+解除结合引起的。
Paired-pulse facilitation (PPF) is a dynamic enhancement of transmitter release considered crucial in CNS information processing. The mechanisms of PPF remain controversial and may differ between synapses. Endogenous Ca2+ buffers such as parvalbumin (PV) and calbindin-D28k (CB) are regarded as important modulators of PPF, with PV acting as an anti-facilitating buffer while saturation of CB can promote PPF. We analysed transmitter release and PPF at intracortical, recurrent Purkinje neuron (PN) to PN synapses, which show PPF during high-frequency activation (200 Hz) and strongly express both PV and CB. We quantified presynaptic Ca2+ dynamics and quantal release parameters in wild-type (WT), and CB and PV deficient mice. Lack of CB resulted in increased volume averaged presynaptic Ca2+ amplitudes and in increased release probability, while loss of PV had no significant effect on these parameters. Unexpectedly, none of the buffers significantly influenced PPF, indicating that neither CB saturation nor residual free Ca2+ ([Ca2+](res)) was the main determinant of PPF. Experimentally constrained, numerical simulations of Ca2+-dependent release were used to estimate the contributions of [Ca2+](res), CB, PV, calmodulin (CaM), immobile buffer fractions and Ca2+ remaining bound to the release sensor after the first of two action potentials (active Ca2+') to PPF. This analysis indicates that PPF at PN-PN synapses does not result from either buffer saturation or [Ca2+](res) but rather from slow Ca2+ unbinding from the release sensor.