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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Analogous Synaptic Plasticity Profiles Emerge from Disparate Channel Combinations
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Analogous Synaptic Plasticity Profiles Emerge from Disparate Channel Combinations

机译：不同通道组合产生类似的突触可塑性曲线

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An open question within the Bienenstock-Cooper-Munro theory for synaptic modification concerns the specific mechanism that is responsible for regulating the sliding modification threshold (SMT). In this conductance-based modeling study on hippocampal pyramidal neurons, we quantitatively assessed the impact of seven ion channels (R- and T-type calcium, fast sodium, delayed rectifier, A-type, and small-conductance calcium-activated (SK) potassium and HCN) and two receptors (AMPAR and NMDAR) on a calcium-dependent Bienenstock-Cooper-Munro-like plasticity rule. Our analysis with R- and T-type calcium channels revealed that differences in their activation-inactivation profiles resulted in differential impacts on how they altered the SMT. Further, we found that the impact of SK channels on the SMT critically depended on the voltage dependence and kinetics of the calcium sources with which they interacted. Next, we considered interactions among all the seven channels and the two receptors through global sensitivity analysis on 11 model parameters. We constructed 20,000 models through uniform randomization of these parameters and found 360 valid models based on experimental constraints on their plasticity profiles. Analyzing these 360 models, we found that similar plasticity profiles could emerge with several nonunique parametric combinations and that parameters exhibited weak pairwise correlations. Finally, we used seven sets of virtual knock-outs on these 360 models and found that the impact of different channels on the SMT was variable and differential. These results suggest that there are several nonunique routes to regulate the SMT, and call for a systematic analysis of the variability and state dependence of the mechanisms underlying metaplasticity during behavior and pathology.
机译：Bienenstock-Cooper-Munro理论中关于突触修饰的一个悬而未决的问题涉及负责调节滑动修饰阈值（SMT）的特定机制。在基于电导的海马锥体神经元建模研究中，我们定量评估了七个离子通道（R和T型钙，快钠，延迟整流器，A型和小电导钙激活（SK）钙和Bienenstock-Cooper-Munro样可塑性规则上的两个受体（AMPAR和NMDAR）。我们对R型和T型钙通道的分析表明，它们的活化-失活曲线上的差异导致对它们改变SMT的方式产生不同的影响。此外，我们发现，SK通道对SMT的影响主要取决于它们与之相互作用的钙源的电压依赖性和动力学。接下来，我们通过对11个模型参数进行全局敏感性分析来考虑所有七个通道与两个受体之间的相互作用。通过对这些参数进行统一随机化，我们构建了20,000个模型，并根据实验可塑性模型的约束条件找到了360个有效模型。通过分析这360个模型，我们发现，几种非唯一的参数组合可能会出现相似的可塑性曲线，并且参数表现出较弱的成对相关性。最后，我们在这360个模型上使用了七组虚拟剔除，发现不同通道对SMT的影响是可变的和差异的。这些结果表明，存在几种调节SMT的非唯一途径，并要求对行为和病理过程中可塑化机制的变异性和状态依赖性进行系统分析。

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