Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish

eLife

Melanie Holmgren¹  Dorina Kallogjeri¹  Lavinia Sheets²  Mark E Warchol³  Kenneth E Hancock⁴  Olga Strelkova⁴  Artur A Indzhykulian⁴  Michael E Ravicz⁴ 

[1] Department of Otolaryngology, Washington University School of Medicine, St Louis, United States;Department of Otolaryngology, Washington University School of Medicine, St Louis, United States;Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States;Department of Otolaryngology, Washington University School of Medicine, St Louis, United States;Department of Neuroscience, Washington University School of Medicine, St Louis, United States;Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, United States;Department of Otolaryngology–Head and Neck Surgery, Harvard Medical School, Boston, United States;

关键词: mechanical damage;    hair cell;    ribbon synapse;    inflammation;    repair;    Zebrafish;   

DOI  :  10.7554/eLife.69264

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 hr 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.

【 授权许可】

CC BY