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Facilitation through Buffer Saturation: Constraints on Endogenous Buffering Properties

机译:通过缓冲液饱和促进:内源缓冲特性的约束

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摘要

Synaptic facilitation (SF) is a ubiquitous form of short-term plasticity, regulating synaptic dynamics on fast timescales. Although SF is known to depend on the presynaptic accumulation of Ca2+, its precise mechanism is still under debate. Recently it has been shown that at certain central synapses SF results at least in part from the progressive saturation of an endogenous Ca2+ buffer (), as proposed by . Using computer simulations, we study the magnitude of SF that can be achieved by a buffer saturation mechanism (BSM), and explore its dependence on the endogenous buffering properties. We find that a high SF magnitude can be obtained either by a global saturation of a highly mobile buffer in the entire presynaptic terminal, or a local saturation of a completely immobilized buffer. A characteristic feature of BSM in both cases is that SF magnitude depends nonmonotonically on the buffer concentration. In agreement with results of , we find that SF grows with increasing distance from the Ca2+ channel cluster, and increases with increasing external Ca2+, [Ca2+]ext, for small levels of [Ca2+]ext. We compare our modeling results with the experimental properties of SF at the crayfish neuromuscular junction, and find that the saturation of an endogenous mobile buffer can explain the observed SF magnitude and its supralinear accumulation time course. However, we show that the BSM predicts slowing of the SF decay rate in the presence of exogenous Ca2+ buffers, contrary to experimental observations at the crayfish neuromuscular junction. Further modeling and data are required to resolve this aspect of the BSM.
机译:突触促进作用(SF)是短期可塑性的一种普遍存在的形式,可以在快速的时间尺度上调节突触的动力学。尽管已知SF依赖于Ca 2 + 的突触前积累,但其确切机制仍在争论中。最近发现,在某些中央突触中,SF至少部分是由内源性Ca 2 + 缓冲液()逐渐饱和所致,如所述。使用计算机模拟,我们研究了可以通过缓冲区饱和机制(BSM)实现的SF的大小,并探讨了其对内源缓冲特性的依赖性。我们发现,可以通过整个突触前末端的高度可移动缓冲区的全局饱和或完全固定的缓冲区的局部饱和来获得高SF大小。两种情况下,BSM的一个特征是SF大小非单调取决于缓冲液浓度。与的结果一致,我们发现SF随着与Ca 2 + 通道簇的距离增加而增长,并且随着外部Ca 2 + ,[Ca 2 + ] ext,用于少量的[Ca 2 + ] ext。我们将我们的建模结果与小龙虾神经肌肉连接处的SF的实验特性进行比较,发现内源移动缓冲液的饱和度可以解释观察到的SF量级及其超线性累积时间过程。然而,我们发现BSM预测在存在外源Ca 2 + 缓冲液的情况下SF衰变速率的减慢,这与小龙虾神经肌肉连接处的实验观察相反。需要进一步的建模和数据来解决BSM的这一方面。

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