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人类听觉神经中的峰电位发生器与细胞信号传导：一项超微结构、超分辨率及基因杂交研究

Spike Generators and Cell Signaling in the Human Auditory Nerve: An Ultrastructural, Super-Resolution, and Gene Hybridization Study.

作者信息

Liu Wei, Luque Maria, Li Hao, Schrott-Fischer Anneliese, Glueckert Rudolf, Tylstedt Sven, Rajan Gunesh, Ladak Hanif, Agrawal Sumit, Rask-Andersen Helge

机构信息

Section of Otolaryngology, Department of Surgical Sciences, Head and Neck Surgery, Uppsala University Hospital, Uppsala, Sweden.

Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.

出版信息

Front Cell Neurosci. 2021 Mar 16;15:642211. doi: 10.3389/fncel.2021.642211. eCollection 2021.

DOI:10.3389/fncel.2021.642211
PMID:33796009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8008129/
Abstract

The human auditory nerve contains 30,000 nerve fibers (NFs) that relay complex speech information to the brain with spectacular acuity. How speech is coded and influenced by various conditions is not known. It is also uncertain whether human nerve signaling involves exclusive proteins and gene manifestations compared with that of other species. Such information is difficult to determine due to the vulnerable, "esoteric," and encapsulated human ear surrounded by the hardest bone in the body. We collected human inner ear material for nanoscale visualization combining transmission electron microscopy (TEM), super-resolution structured illumination microscopy (SR-SIM), and RNA-scope analysis for the first time. Our aim was to gain information about the molecular instruments in human auditory nerve processing and deviations, and ways to perform electric modeling of prosthetic devices. Human tissue was collected during trans-cochlear procedures to remove petro-clival meningioma after ethical permission. Cochlear neurons were processed for electron microscopy, confocal microscopy (CM), SR-SIM, and high-sensitive hybridization for labeling single mRNA transcripts to detect ion channel and transporter proteins associated with nerve signal initiation and conductance. Transport proteins and RNA transcripts were localized at the subcellular level. Hemi-nodal proteins were identified beneath the inner hair cells (IHCs). Voltage-gated ion channels (VGICs) were expressed in the spiral ganglion (SG) and axonal initial segments (AISs). Nodes of Ranvier (NR) expressed Nav1.6 proteins, and encoding genes critical for inter-cellular coupling were disclosed. Our results suggest that initial spike generators are located beneath the IHCs in humans. The first NRs appear at different places. Additional spike generators and transcellular communication may boost, sharpen, and synchronize afferent signals by cell clusters at different frequency bands. These instruments may be essential for the filtering of complex sounds and may be challenged by various pathological conditions.

摘要

人类听觉神经包含30000根神经纤维，它们能以惊人的敏锐度将复杂的语音信息传递给大脑。语音是如何编码以及受各种条件影响的尚不清楚。与其他物种相比，人类神经信号传导是否涉及独特的蛋白质和基因表现也不确定。由于人体耳朵脆弱、“深奥”且被身体最坚硬的骨头包裹，很难确定此类信息。我们首次结合透射电子显微镜（TEM）、超分辨率结构光照显微镜（SR-SIM）和RNA原位杂交分析收集人类内耳材料用于纳米级可视化。我们的目的是获取有关人类听觉神经处理中的分子工具和偏差以及人工耳蜗装置电建模方法的信息。在获得伦理许可后，在经耳蜗手术切除岩斜脑膜瘤的过程中收集人体组织。对耳蜗神经元进行电子显微镜、共聚焦显微镜（CM）、SR-SIM和高灵敏度杂交处理，以标记单个mRNA转录本，检测与神经信号起始和传导相关的离子通道和转运蛋白。转运蛋白和RNA转录本定位在亚细胞水平。在内毛细胞（IHC）下方鉴定出半节点蛋白。电压门控离子通道（VGIC）在螺旋神经节（SG）和轴突起始段（AIS）中表达。郎飞结（NR）表达Nav1.6蛋白，并揭示了对细胞间耦合至关重要的编码基因。我们的结果表明，人类最初的动作电位发生器位于IHC下方。第一个NR出现在不同位置。额外的动作电位发生器和跨细胞通讯可能通过不同频段的细胞簇增强、锐化和同步传入信号。这些工具可能对复杂声音的滤波至关重要，并且可能受到各种病理状况的挑战。

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