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 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.
Highlights
Hair cells are the sensory receptors of the inner ear and lateral-line organs that detect sound, orientation, and motion
To mechanically damage hair cells of lateral-line organs in free-swimming 7-day-old zebrafish, we developed a stimulation protocol using an electrodynamic shaker to create a strong water wave stimulus (Fig.1 A)
The frequency used for mechanical stimulation was selected and further verified based on previous studies showing 60 Hz to be within the optimal upper frequency range of mechanical sensitivity of superficial posterior lateral-line neuromasts, which respond maximally between 10-60 Hz, but a suboptimal frequency for hair cells of the anterior macula of the inner ear (Levi, Akanyeti, Ballo, & Liao, 2015; Trapani & Nicolson, 2010; Weeg, Fay, & Bass, 2002)
Summary
Hair cells are the sensory receptors of the inner ear and lateral-line organs that detect sound, orientation, and motion They transduce these stimuli through deflection of stereocilia, which opens mechanically-gated cation channels (LeMasurier & Gillespie, 2005; Qiu & Muller, 2018) and drives subsequent transmission of sensory information via excitatory glutamatergic synapses (Glowatzki & Fuchs, 2002). In order to model physical damage to hair cell organs in zebrafish lateral line, we developed a protocol to mechanically stimulate the lateral line of free-swimming 7-day-old larvae Using this protocol, we were able to induce mechanical injury to lateral-line organs that resembled the trauma observed in the mammalian cochlea following acoustic overstimulation. Neuromasts showed partial recovery of afferent innervation within 2 hours following exposure and completely recovered hair-cell morphology and FM1-43 uptake within 4 hours These results support that mechanically injured neuromasts show similar features of damage observed in noise exposed ears, yet rapidly repair
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