论文标题

小型DRG神经元的9D模型的计算分析

Computational analysis of a 9D model for a small DRG neuron

论文作者

Verma, Parul, Kienle, Achim, Flockerzi, Dietrich, Ramkrishna, Doraiswami

论文摘要

小背根神经节(DRG)神经元是负责感应疼痛的主要伤害感受器。阐明其动力学对于理解和控制疼痛至关重要。为此,我们在本文中介绍了小型DRG神经元模型的数值分叉分析。该模型是Hodgkin-Huxley类型的,具有9个状态变量。它由Na $ \ Mathrm {_V} $ 1.7和Na $ \ Mathrm {_V} $ 1.8钠通道,泄漏通道,延迟的整流器钾和A-Type瞬态钾通道组成。该模型的动力学在很大程度上取决于电压门控离子通道和外部电流的最大电导率,这可以通过实验进行调整。我们表明,神经元动力学对Na $ \ Mathrm {_V} $ 1.8通道最大电导率($ \ bar {g} _ {1.8} $)最敏感。数值分叉分析表明,取决于$ \ bar {g} _ {1.8} $,外部电流,不同的参数区域可以通过稳定的稳态,稳定的混合模式振荡(MMOS)以及稳定的稳态稳定状态和稳定的周期性射击行动电势射击。我们说明和讨论这些不同制度之间的过渡。我们进一步分析了MMO的行为。在该区域内,分叉分析显示了一系列分离的周期溶液分支,每个周期具有一个较大的动作电位和许多小幅度峰。仔细检查表明,在这些周期性的MMO分支之间,形成Farey序列之间更复杂的串联MMO。最后,我们还发现带有基质振荡的小型解决方案窗口似乎是混乱的。此处发现的动态模式是不同参数的函数,其中包含转化重要性的信息,因为它们与疼痛感觉的关系及其强度是控制疼痛的潜在洞察力。

Small dorsal root ganglion (DRG) neurons are primary nociceptors which are responsible for sensing pain. Elucidation of their dynamics is essential for understanding and controlling pain. To this end, we present a numerical bifurcation analysis of a small DRG neuron model in this paper. The model is of Hodgkin-Huxley type and has 9 state variables. It consists of a Na$\mathrm{_v}$1.7 and a Na$\mathrm{_v}$1.8 sodium channel, a leak channel, a delayed rectifier potassium and an A-type transient potassium channel. The dynamics of this model strongly depends on the maximal conductances of the voltage-gated ion channels and the external current, which can be adjusted experimentally. We show that the neuron dynamics are most sensitive to the Na$\mathrm{_v}$1.8 channel maximal conductance ($\bar{g}_{1.8}$). Numerical bifurcation analysis shows that depending on $\bar{g}_{1.8}$ and the external current, different parameter regions can be identified with stable steady states, periodic firing of action potentials, mixed-mode oscillations (MMOs), and bistability between stable steady states and stable periodic firing of action potentials. We illustrate and discuss the transitions between these different regimes. We further analyze the behavior of MMOs. Within this region, bifurcation analysis shows a sequence of isolated periodic solution branches with one large action potential and a number of small amplitude peaks per period. A closer inspection reveals more complex concatenated MMOs in between these periodic MMOs branches, forming Farey sequences. Lastly, we also find small solution windows with aperiodic oscillations, which seem to be chaotic. The dynamical patterns found here as a function of different parameters contain information of translational importance as their relation to pain sensation and its intensity is a potential source of insight into controlling pain.

扫码加入交流群

加入微信交流群

微信交流群二维码

扫码加入学术交流群,获取更多资源