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A Comparison between Direct and Indirect Measurements ofNeurotransmitter Vesicle Release Dynamics: A computational Study

机译:直接和间接测量的比较神经递质囊泡释放动力学:一项计算研究。

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摘要

Presynaptic vesicular release of neurotransmitters is a stochastic process involving complex mechanisms triggered by an elevation of calcium concentration. The mechanisms behind neurotransmitters release play a critical role in synaptic function and plasticity. Understanding its properties, both in term of its dynamics and its underlying mechanisms, may therefore help further our understanding of synaptic plasticity. However, measuring vesicle release dynamics is experimentally challenging. One experimental protocol used to determine the dynamic properties of vesicle release is to measure postsynaptic current. However, this method inherently not only captures properties of the release itself, but also the contributions from the postsynaptic receptors. Here we propose to use a synapse simulation platform known as EONS/RHENOMS to capture the functional properties of vesicle release, separate from the dynamics known to be associated with postsynaptic receptors, and compare the results with those determined experimentally. We find that despite attempts to reduce interference of postsynaptic dynamics, the receptor channel properties, particularly desensitization, may influence the overall measured results significantly. Re-estimating release rate by taking into account the contributions ofpostsynaptic receptors may give further insight into release dynamics andfurther our overall understanding on synaptic plasticity.
机译:突触前神经递质的囊泡释放是一个随机过程,涉及由钙浓度升高触发的复杂机制。神经递质释放的机制在突触功能和可塑性中起关键作用。因此,从动力学及其潜在机制的角度了解其特性,可能有助于我们进一步了解突触可塑性。然而,测量囊泡释放动力学在实验上具有挑战性。用于确定囊泡释放的动态特性的一种实验方案是测量突触后电流。然而,该方法固有地不仅捕获释放本身的性质,而且还捕获突触后受体的贡献。在这里,我们建议使用称为EONS / RHENOMS的突触模拟平台来捕获囊泡释放的功能特性,与已知与突触后受体相关的动力学分开,并将结果与​​实验确定的结果进行比较。我们发现尽管尝试减少突触后动力学的干扰,但受体通道的特性,特别是脱敏,可能会显着影响总体测量结果。通过考虑以下因素的贡献重新估算释放率突触后受体可能会进一步了解释放动力学和进一步了解了我们对突触可塑性的整体理解。

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