Kostrikov Serhii, Hjortkjaer Jens, Dau Torsten, Corfas Gabriel, Liberman Leslie D, Liberman M Charles
Department of Health Technology, Centre for Auditory Neuroscience, Hearing Systems, Technical University of Denmark, Lyngby, Denmark.
Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, United States.
Hear Res. 2025 Feb;456:109172. doi: 10.1016/j.heares.2024.109172. Epub 2024 Dec 18.
Auditory-nerve fibers (ANFs) from a given cochlear region can vary in threshold sensitivity by up to 60 dB, corresponding to a 1000-fold difference in stimulus level, although each fiber innervates a single inner hair cell (IHC) via a single synapse. ANFs with high-thresholds also have low spontaneous rates (SRs) and synapse on the side of the IHC closer to the modiolus, whereas the low-threshold, high-SR fibers synapse on the side closer to the pillar cells. Prior biophysical work has identified modiolar-pillar differences in both pre- and post-synaptic properties, but a comprehensive explanation for the wide range of sensitivities remains elusive. Here, in guinea pigs, we used immunostaining for several neuronal markers, including Caspr, a key protein in nodes of Ranvier, to reveal a novel modiolar-pillar gradient in the location of the first ANF heminodes, presumed to be the site of the spike generator, just outside the sensory epithelium. Along the cochlea, from apex to base, the unmyelinated terminal dendrites of modiolar ANFs were 2-4 times longer than those of pillar ANFs. This modiolar-pillar gradient in dendritic length, coupled with the 2-4 fold smaller caliber of modiolar dendrites seen in prior single-fiber labeling studies, suggests there could be a large difference in the number of length constants between the synapse and the spike initiation zone for low- vs high-SR fibers. The resultant differences in attenuation of post-synaptic potentials propagating along these unmyelinated dendrites could be a key contributor to the observed range of threshold sensitivities among ANFs.
来自给定耳蜗区域的听神经纤维(ANF)的阈值敏感性差异可达60分贝,这相当于刺激强度相差1000倍,尽管每条纤维通过单个突触支配单个内毛细胞(IHC)。高阈值的ANF的自发发放率(SR)也较低,并且在更靠近蜗轴的内毛细胞一侧形成突触,而低阈值、高SR的纤维则在更靠近柱细胞的一侧形成突触。先前的生物物理学研究已经确定了突触前和突触后特性在蜗轴侧和柱细胞侧的差异,但对于如此广泛的敏感性差异,仍缺乏全面的解释。在这里,我们在豚鼠中使用了几种神经元标记物进行免疫染色,包括Caspr(郎飞结中的一种关键蛋白),以揭示第一个ANF半结位置上存在一种新的蜗轴 - 柱细胞梯度,推测该半结是动作电位起始位点,位于感觉上皮之外。沿着耳蜗从顶端到基部,蜗轴侧ANF的无髓鞘终末树突比柱细胞侧ANF的长2 - 4倍。这种树突长度的蜗轴 - 柱细胞梯度,再加上先前单纤维标记研究中观察到的蜗轴侧树突直径小2 - 4倍的情况,表明低SR纤维与高SR纤维在突触和动作电位起始区之间的长度常数数量可能存在很大差异。沿这些无髓鞘树突传播的突触后电位衰减的差异可能是导致观察到的ANF阈值敏感性范围的关键因素。