Department of Otolaryngology, The Ohio State University, Columbus, OH, USA.
Department of Otolaryngology, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
Neuroscience. 2023 Mar 15;514:25-37. doi: 10.1016/j.neuroscience.2023.01.037. Epub 2023 Feb 3.
Cellular morphology and synaptic configuration are key determinants of neuronal function and are often modified under pathological conditions. In the first nucleus of the central auditory system, the cochlear nucleus (CN), principal bushy neurons specialize in processing temporal information of sound critical for hearing. These neurons alter their physiological properties during aging that contribute to age-related hearing loss (ARHL). The structural basis of such changes remains unclear, especially age-related modifications in their dendritic morphology and the innervating auditory nerve (AN) synapses. Using young (2-5 months) and aged (28-33 months) CBA/CaJ mice of either sex, we filled individual bushy neurons with fluorescent dye in acute brain slices to characterize their dendritic morphology, followed by immunostaining against vesicular glutamate transporter 1 (VGluT1) and calretinin (CR) to identify innervating AN synapses. We found that dendritic morphology of aged bushy neurons had significantly reduced complexity, suggesting age-dependent dendritic degeneration, especially in neurons with predominantly non-CR-expressing synapses on the soma. These dendrites were innervated by AN bouton synapses, which were predominantly non-CR-expressing in young mice but had increased proportion of CR-expressing synapses in old mice. While somatic AN synapses degenerated substantially with age, as quantified by VGluT1-labeled puncta volume, no significant difference was observed in the total volume of dendritic synapses between young and old mice. Consequently, synaptic density on dendrites was significantly higher in old mice. The findings suggest that dendritic degeneration and altered synaptic innervation in bushy neurons during aging may underlie their changed physiological activity and contribute to the development of ARHL.
细胞形态和突触结构是神经元功能的关键决定因素，它们在病理条件下常常发生改变。在中枢听觉系统的第一个核团——耳蜗核（CN）中，主要的毛细胞神经元专门处理声音的时间信息，这对听觉至关重要。这些神经元在衰老过程中改变其生理特性，这是与年龄相关的听力损失（ARHL）的原因之一。这些变化的结构基础仍不清楚，特别是它们树突形态和支配听神经（AN）突触的与年龄相关的改变。我们使用年轻（2-5 个月）和年老（28-33 个月）的 CBA/CaJ 雌雄小鼠，在急性脑片中用荧光染料填充单个毛细胞，以描述其树突形态，然后用针对囊泡谷氨酸转运体 1（VGluT1）和钙结合蛋白（CR）的免疫染色来识别支配 AN 突触的突触。我们发现，年老的毛细胞神经元的树突形态复杂性显著降低，表明存在与年龄相关的树突退化，尤其是在那些主要表达非 CR 的突触位于胞体上的神经元中。这些树突被 AN 末梢突触支配，在年轻小鼠中这些突触主要是非 CR 表达，但在年老小鼠中则增加了 CR 表达的突触比例。虽然 AN 突触随着年龄的增长而显著退化，如 VGluT1 标记的点状体积所量化的，但年轻和年老小鼠之间树突突触的总体积没有显著差异。因此，年老小鼠的树突上的突触密度显著增加。这些发现表明，毛细胞神经元在衰老过程中发生的树突退化和突触支配的改变可能是其生理活动改变的基础，并导致 ARHL 的发展。
