Heshmat Amirreza, Sajedi Sogand, Johnson Chacko Lejo, Fischer Natalie, Schrott-Fischer Anneliese, Rattay Frank
Faculty of Mathematics and Geoinformation, Institute for Analysis and Scientific Computing, Vienna University of Technology, Vienna, Austria.
Laboratory for Inner Ear Biology, Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
Front Neurosci. 2020 Nov 19;14:599868. doi: 10.3389/fnins.2020.599868. eCollection 2020.
Due to limitations of human studies, detailed computational models enable understanding the neural signaling in the degenerated auditory system and cochlear implants (CIs). Four human cochleae were used to quantify hearing levels depending on dendritic changes in diameter and myelination thickness from type I of the auditory nerve fibers (ANFs). Type I neurons transmit the auditory information as spiking pattern from the inner hair cells (IHCs) to the cochlear nucleus. The impact of dendrite diameter and degree of myelination on neural signal transmission was simulated for (1) synaptic excitation via IHCs and (2) stimulation from CI electrodes. An accurate three-dimensional human cochlear geometry, along with 30 auditory pathways, mimicked the CI environment. The excitation properties of electrical potential distribution induced by two CI were analyzed. Main findings: (1) The unimodal distribution of control dendrite diameters becomes multimodal for hearing loss cases; a group of thin dendrites with diameters between 0.3 and 1 μm with a peak at 0.5 μm appeared. (2) Postsynaptic currents from IHCs excite such thin dendrites easier and earlier than under control conditions. However, this advantage is lost as their conduction velocity decreases proportionally with the diameter and causes increased spike latency and jitter in soma and axon. Firing probability reduces through the soma passage due to the low intracellular current flow in thin dendrites during spiking. (3) Compared with dendrite diameter, variations in myelin thickness have a small impact on spiking performance. (4) Contrary to synaptic excitation, CIs cause several spike initiation sites in dendrite, soma region, and axon; moreover, fiber excitability reduces with fiber diameter. In a few cases, where weak stimuli elicit spikes of a target neuron (TN) in the axon, dendrite diameter reduction has no effect. However, in many cases, a spike in a TN is first initiated in the dendrite, and consequently, dendrite degeneration demands an increase in threshold currents. (5) Threshold currents of a TN and co-stimulation of degenerated ANFs in other frequency regions depend on the electrode position, including its distance to the outer wall, the cochlear turn, and the three-dimensional pathway of the TN.
由于人体研究的局限性，详细的计算模型有助于理解退化听觉系统和人工耳蜗（CI）中的神经信号传导。使用四个人类耳蜗来根据听觉神经纤维（ANF）I型的树突直径和髓鞘厚度变化来量化听力水平。I型神经元以尖峰模式将听觉信息从内毛细胞（IHC）传递到耳蜗核。模拟了树突直径和髓鞘化程度对神经信号传递的影响，包括（1）通过IHC的突触兴奋和（2）CI电极的刺激。精确的三维人类耳蜗几何结构以及30条听觉通路模拟了CI环境。分析了两种CI引起的电位分布的激发特性。主要发现：（1）听力损失病例中，对照树突直径的单峰分布变为多峰分布；出现了一组直径在0.3至1μm之间、峰值在0.5μm的细树突。（2）与对照条件相比，来自IHC的突触后电流更容易且更早地激发此类细树突。然而，随着它们的传导速度与直径成比例下降，这种优势丧失，导致胞体和轴突中的峰值潜伏期增加和抖动增加。由于细树突在放电时细胞内电流低，通过胞体通道的放电概率降低。（3）与树突直径相比，髓鞘厚度的变化对放电性能影响较小。（4）与突触兴奋相反，CI在树突、胞体区域和轴突中引起多个放电起始位点；此外，纤维兴奋性随纤维直径降低。在少数情况下，弱刺激在轴突中引发目标神经元（TN）的尖峰，树突直径减小没有影响。然而，在许多情况下，TN中的尖峰首先在树突中引发，因此，树突退化需要增加阈值电流。（5）TN的阈值电流以及其他频率区域中退化ANF的共刺激取决于电极位置，包括其到外壁的距离、耳蜗螺旋以及TN的三维路径。
