Modeling of sustained spontaneous network oscillations of a sexually dimorphic brainstem nucleus: the role of potassium equilibrium potential
Modeling of sustained spontaneous network oscillations of a sexually dimorphic brainstem nucleus: the role of potassium equilibrium potential
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DOI：
10.1007/s10827-021-00789-2
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发表时间：
2021-05-25
影响因子：
1.2
通讯作者：
Zupanc, Gunther K. H.
中科院分区：
文献类型：
--
作者：
Hartman, Daniel;Lehotzky, David;Zupanc, Gunther K. H.
中枢神经系统的内在振荡器在神经控制节律行为中起着突出的作用，但对离子环境如何调节其输出模式知之甚少。一个强有力的系统来解决这个问题是起搏核的弱电鱼类Apteronotus leptorhynchus。平均由87个起搏细胞和20个中继细胞组成的神经网络产生强直性振荡，男性的频率高于女性。以前的实证研究表明，这种性二态性的发展和维持通过缓冲细胞外K+的大量网状星形胶质细胞包裹的起搏器和中继细胞的调制。在这里，我们构建了一个可以产生持续自发振荡的神经网络模型。敏感性分析揭示了钾平衡电位，E-K（作为细胞外K+浓度的代理），和相应的体细胞通道电导振荡频率和振幅的关键决定因素。在起搏核网络模型和离体起搏细胞和中继细胞模型中，频率随E-K的增加几乎呈线性增加，而振幅随E-K的增加呈非线性下降。我们的模拟预测，这种频率的增加主要是由在一个振荡周期的最小K+电导的移位。这个最小值在更负的E-K时接近于零，在更小的负E-K时收敛到相应的最大值。这使得静息膜电位更接近阈值电位，在该阈值电位下电压门控Na+通道变得活跃，从而增加起搏器和中继细胞的兴奋性，并因此增加频率。
Intrinsic oscillators in the central nervous system play a preeminent role in the neural control of rhythmic behaviors, yet little is known about how the ionic milieu regulates their output patterns. A powerful system to address this question is the pacemaker nucleus of the weakly electric fish Apteronotus leptorhynchus. A neural network comprised of an average of 87 pacemaker cells and 20 relay cells produces tonic oscillations, with higher frequencies in males compared to females. Previous empirical studies have suggested that this sexual dimorphism develops and is maintained through modulation of buffering of extracellular K+ by a massive meshwork of astrocytes enveloping the pacemaker and relay cells. Here, we constructed a model of this neural network that can generate sustained spontaneous oscillations. Sensitivity analysis revealed the potassium equilibrium potential, E-K (as a proxy of extracellular K+ concentration), and corresponding somatic channel conductances as critical determinants of oscillation frequency and amplitude. In models of both the pacemaker nucleus network and isolated pacemaker and relay cells, the frequency increased almost linearly with E-K, whereas the amplitude decreased nonlinearly with increasing E-K. Our simulations predict that this frequency increase is largely caused by a shift in the minimum K+ conductance over one oscillation period. This minimum is close to zero at more negative E-K, converging to the corresponding maximum at less negative E-K. This brings the resting membrane potential closer to the threshold potential at which voltage-gated Na+ channels become active, increasing the excitability, and thus the frequency, of pacemaker and relay cells.