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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Our revised manuscript provides additional recovery data supporting that disrupted neuromast hair cells are rapidly repaired following mechanical damage (Fig 10). In addition, to accommodate nested data and ensure statistical rigor, our data has been reanalyzed by Dr. Dorina Kallogjeri, a research statistician affiliated with our department. Using an unconditional model, she determined ∼35% of variability in hair cell number ∼25% variability in innervation could be accounted for by the fish in the experiment. She therefore used a multilevel model to test statistical differences between conditions and groups.
