Zhang Qiang, Dai Yue, Zhou Junya, Ge Renkai, Hua Yiyun, Powers Randall K, Binder Marc D
Shanghai Key Laboratory of Multidimensional Information Processing, School of Communication and Electronic Engineering, East China Normal University, Shanghai, China.
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, School of Physical Education and Health Care, East China Normal University, Shanghai, China.
Front Physiol. 2022 Aug 23;13:955566. doi: 10.3389/fphys.2022.955566. eCollection 2022.
Oscillations in membrane potential induced by synaptic inputs and intrinsic ion channel activity play a role in regulating neuronal excitability, but the precise mechanisms underlying their contributions remain largely unknown. Here we used electrophysiological and modeling approaches to investigate the effects of Gaussian white noise injected currents on the membrane properties and discharge characteristics of hypoglossal (HG) motoneurons in P16-21 day old rats. We found that the noise-induced membrane potential oscillations facilitated spike initiation by hyperpolarizing the cells' voltage threshold by 3.1 ± 1.0 mV and reducing the recruitment current for the tonic discharges by 0.26 ± 0.1 nA, on average ( = 59). Further analysis revealed that the noise reduced both recruitment and decruitment currents by 0.26 ± 0.13 and 0.33 ± 0.1 nA, respectively, and prolonged the repetitive firing. The noise also increased the slopes of frequency-current (F-I) relationships by 1.1 ± 0.2 Hz/nA. To investigate the potential mechanisms underlying these findings, we constructed a series of HG motoneuron models based on their electrophysiological properties. The models consisted of five compartments endowed with transient sodium (NaT), delayed-rectify potassium [K(DR)], persistent sodium (NaP), calcium-activated potassium [K(AHP)], L-type calcium (CaL) and H-current channels. In general, all our experimental results could be well fitted by the models, however, a modification of standard Hodgkin-Huxley kinetics was required to reproduce the changes in the F-I relationships and the prolonged discharge firing. This modification, corresponding to the noise generated by the stochastic flicker of voltage-gated ion channels (channel flicker, CF), was an adjustable sinusoidal function added to kinetics of the channels that increased their sensitivity to subthreshold membrane potential oscillations. Models with CF added to NaP and CaL channels mimicked the noise-induced alterations of membrane properties, whereas models with CF added to NaT and K(DR) were particularly effective in reproducing the noise-induced changes for repetitive firing observed in the real motoneurons. Further analysis indicated that the modified channel kinetics enhanced NaP- and CaL-mediated inward currents thus increasing the excitability and output of HG motoneurons, whereas they produced relatively small changes in NaT and K(DR), thus balancing these two currents and triggering variability of repetitive firing. This study provided insight into the types of membrane channel mechanisms that might underlie oscillation-induced alterations of neuronal excitability and motor output in rat HG motoneurons.
由突触输入和内在离子通道活动诱导的膜电位振荡在调节神经元兴奋性中发挥作用，但其贡献背后的确切机制在很大程度上仍然未知。在这里，我们使用电生理和建模方法来研究注入高斯白噪声电流对16 - 21日龄大鼠舌下（HG）运动神经元的膜特性和放电特性的影响。我们发现，噪声诱导的膜电位振荡通过将细胞的电压阈值超极化3.1±1.0 mV并平均将强直放电的募集电流降低0.26±0.1 nA（n = 59）来促进动作电位起始。进一步分析表明，噪声分别将募集电流和去募集电流降低了0.26±0.13和0.33±0.1 nA，并延长了重复放电。噪声还使频率 - 电流（F - I）关系的斜率增加了1.1±0.2 Hz/nA。为了研究这些发现背后的潜在机制，我们根据其电生理特性构建了一系列HG运动神经元模型。这些模型由五个具有瞬时钠（NaT）、延迟整流钾[K(DR)]、持续性钠（NaP）、钙激活钾[K(AHP)]、L型钙（CaL）和H电流通道的隔室组成。总体而言，我们所有的实验结果都能被模型很好地拟合，然而，需要对标准霍奇金 - 赫胥黎动力学进行修改以重现F - I关系的变化和延长的放电发放。这种修改对应于电压门控离子通道的随机闪烁产生的噪声（通道闪烁，CF），是一个添加到通道动力学中的可调正弦函数，增加了它们对阈下膜电位振荡的敏感性。在NaP和CaL通道中添加CF的模型模拟了噪声诱导的膜特性改变，而在NaT和K(DR)中添加CF的模型在重现真实运动神经元中观察到的噪声诱导的重复放电变化方面特别有效。进一步分析表明，修改后的通道动力学增强了NaP和CaL介导的内向电流，从而增加了HG运动神经元的兴奋性和输出，而它们在NaT和K(DR)中产生的变化相对较小，可以平衡这两种电流并触发重复放电的变异性。这项研究深入了解了大鼠HG运动神经元中振荡诱导的神经元兴奋性和运动输出改变可能背后的膜通道机制类型。
