Age-dependent structural reorganization of utricular ribbon synapses

Susann Michanski; Timo Henneck; Mohona Mukhopadhyay; Anna M Steyer; Paola Agüi Gonzalez; Katharina Grewe; Peter Ilgen; Mehmet Gültas; Eugenio F Fornasiero; Stefan Jakobs; Wiebke Möbius; Christian Vogl; Tina Pangršič; Silvio O Rizzoli; Carolin Wichmann

doi:10.3389/fcell.2023.1178992

Age-dependent structural reorganization of utricular ribbon synapses

Front Cell Dev Biol. 2023 Aug 10:11:1178992. doi: 10.3389/fcell.2023.1178992. eCollection 2023.

Authors

Susann Michanski^{1

2

3}, Timo Henneck⁴, Mohona Mukhopadhyay⁵, Anna M Steyer^{6

7}, Paola Agüi Gonzalez⁸, Katharina Grewe⁸, Peter Ilgen^{9

10

11}, Mehmet Gültas¹², Eugenio F Fornasiero⁸, Stefan Jakobs^{9

10

11}, Wiebke Möbius^{3

6}, Christian Vogl^{2

13

14}, Tina Pangršič^{2

3

5}, Silvio O Rizzoli⁸, Carolin Wichmann^{1

2

3}

Affiliations

¹ Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience, InnerEarLab and Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
² Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.
³ Multiscale Bioimaging Cluster of Excellence (MBExC), University of Göttingen, Göttingen, Germany.
⁴ Biology Bachelor Program, University of Göttingen, Göttingen, Germany.
⁵ Experimental Otology Group, InnerEarLab, Department of Otolaryngology, Institute for Auditory Neuroscience, University Medical Center Göttingen, Göttingen, Germany.
⁶ Electron Microscopy-City Campus, Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
⁷ Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Göttingen, Göttingen, Germany.
⁸ Department for Neuro-and Sensory Physiology, University Medical Center Göttingen, Center for Biostructural Imaging of Neurodegeneration (BIN), Göttingen, Germany.
⁹ Clinic of Neurology, University Medical Center Göttingen, Göttingen, Germany.
¹⁰ Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
¹¹ Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Translational Neuroinflammation and Automated Microscopy TNM, Göttingen, Germany.
¹² Faculty of Agriculture, South Westphalia University of Applied Sciences, Soest, Germany.
¹³ Presynaptogenesis and Intracellular Transport in Hair Cells Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.
¹⁴ Auditory Neuroscience Group, Institute of Physiology, Medical University Innsbruck, Innsbruck, Austria.

Abstract

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.

Keywords: aging; ribbon synapse; synaptogenesis; utricle; vestibular hair cells.

Grants and funding

This work was funded by German Research Foundation grants (Deutsche Forschungsgemeinschaft): Collaborative Research Center 889 [Projects A07 (CW), B08 to CV, and B09 to TP] and TP, SJ, WM, and CW were further supported by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy–EXC 2067/1-390729940. SOR, SJ, and CW were further funded by German Research Foundation grants: Collaborative Research Center 1286 [Projects A04 to CW, A05 to SJ, and A03 to SOR]. Part of this work (AMS) was funded by the Cluster of Excellence and DFG Research Center Nanoscale Microscopy and Molecular Physiology of the Brain [Research field A1 (WM)] and by the Deutsche Forschungsgemeinschaft (DFG) (FOR2848, MO 1082/1-2, project 08 to WM). CV was an Otto Creutzfeldt-Fellow of the Elisabeth and Helmut Uhl Foundation. MM and TP are funded via the BMBF and MWK (Bundesministerium für Bildung und Forschung and Niedersächsisches Ministerium für Wissenschaft und Kultur; Professorinnenprogramm III, 22-38 285/1-3-12-1 and 22-76251-99-17/19 to TP). EFF was supported by a Schram Stiftung (T0287/35359/2020) and a DFG grant (FO 1342/1-3). SOR, KG, and PAG were supported by a DFG grant (RI 1967/10-1, NeuroNex). The position of SM was partially paid by a grant of the “Niedersächsisches Vorab” to Tobias Moser.