Michanski Susann, Henneck Timo, Mukhopadhyay Mohona, Steyer Anna M, Gonzalez Paola Agüi, Grewe Katharina, Ilgen Peter, Gültas Mehmet, Fornasiero Eugenio F, Jakobs Stefan, Möbius Wiebke, Vogl Christian, Pangršič Tina, Rizzoli Silvio O, Wichmann Carolin
Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience, InnerEarLab and Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.
Front Cell Dev Biol. 2023 Aug 10;11:1178992. doi: 10.3389/fcell.2023.1178992. eCollection 2023.
In mammals, spatial orientation is synaptically-encoded by sensory hair cells of the vestibular labyrinth. Vestibular hair cells (VHCs) harbor synaptic ribbons at their presynaptic active zones (AZs), which play a critical role in molecular scaffolding and facilitate synaptic release and vesicular replenishment. With advancing age, the prevalence of vestibular deficits increases; yet, the underlying mechanisms are not well understood and the possible accompanying morphological changes in the VHC synapses have not yet been systematically examined. We investigated the effects of maturation and aging on the ultrastructure of the ribbon-type AZs in murine utricles using various electron microscopic techniques and combined them with confocal and super-resolution light microscopy as well as metabolic imaging up to 1 year of age. In older animals, we detected predominantly in type I VHCs the formation of floating ribbon clusters, mostly consisting of newly synthesized ribbon material. Our findings suggest that VHC ribbon-type AZs undergo dramatic structural alterations upon aging.
在哺乳动物中，空间定向由前庭迷路的感觉毛细胞通过突触进行编码。前庭毛细胞（VHCs）在其突触前活动区（AZs）含有突触 ribbons，这些 ribbons 在分子支架中起关键作用，并促进突触释放和囊泡补充。随着年龄的增长，前庭功能障碍的患病率增加；然而，其潜在机制尚未完全了解，VHC 突触可能伴随的形态变化也尚未得到系统研究。我们使用各种电子显微镜技术研究了成熟和衰老对小鼠椭圆囊 ribbon 型 AZs 超微结构的影响，并将其与共聚焦和超分辨率光学显微镜以及长达 1 年的代谢成像相结合。在老年动物中，我们主要在 I 型 VHCs 中检测到漂浮 ribbon 簇的形成，这些簇主要由新合成的 ribbon 材料组成。我们的研究结果表明，VHC ribbon 型 AZs 在衰老时会发生显著的结构改变。
