Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish
- Washington University School of Medicine in St Louis, United States
- Massachusetts Eye and Ear, United States
- Washington University School of Medicine in St. Louis, United States
- Harvard Medical School, United States
- Washington University School of Medicine, United States
Abstract
Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hours displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 4 , and 7.
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Author details
Funding
National Institute on Deafness and Other Communication Disorders (R01DC016066)
- Lavinia Sheets
National Institute on Deafness and Other Communication Disorders (R01DC017166)
- Artur A Indzhykulian
National Institute on Deafness and Other Communication Disorders (R01DC006283)
- Mark E Warchol
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed with the approval of the Institutional Animal Care and Use Committee of Washington University School of Medicine in St. Louis (protocol no. 20-0158) and in accordance with NIH guidelines for use of zebrafish.
Copyright
© 2021, Holmgren et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish
eLife 10:e69264.
https://doi.org/10.7554/eLife.69264
