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bioRxiv · 10.1101/2025.01.07.631771

Noise-induced hearing loss enhances Ca2+-dependent spontaneous bursting activity in lateralcochlear efferents

Hong, H.·Trussell, L. O.
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Abstract

Exposure to loud and/or prolonged noise damages cochlear hair cells and triggers downstream changes in synaptic and electrical activity in multiple brain regions, resulting in hearing loss and altered speech comprehension. It remains unclear however whether or not noise exposure also compromises the cochlear efferent system, a feedback pathway in the brain that fine-tunes hearing sensitivity in the cochlea. We examined the effects of noise-induced hearing loss on the spontaneous action potential (AP) firing pattern in mouse lateral olivocochlear (LOC) neurons. This spontaneous firing exhibits a characteristic burst pattern dependent on Ca2+ channels, and we therefore also examined the effects of noise-induced hearing loss on the function of these and other ion channels. The burst pattern was sustained by an interaction between inactivating Ca2+ currents contributed largely by L-type channels, and steady outward currents mediated by Ba2+-sensitive inwardly-rectifying and two-pore domain K+ channels. One week following exposure to loud broadband noise, hearing thresholds were significantly elevated, and the duration of AP bursts was increased, likely as a result of an enhanced Ca2+ current. Additional effects of noise-induced hearing loss included alteration of Ca2+-dependent inactivation of Ca2+ currents and a small elevation of outward K+ currents. We propose that noise-induced hearing loss enhances efferent activity and may thus amplify the release of neurotransmitters and neuromodulators (i.e., neuropeptides), potentially altering sensory coding within the damaged cochlea. Significance StatementAlthough the effects of noise-induced hearing loss on the auditory afferent system have been extensively studied, little is known about its impact on the auditory efferent system, which modulates hearing sensitivity via feedback from the brain. Additionally, while Ca2+ channels are related to numerous neurological diseases, their involvement in auditory disorders is underexplored. This study bridges these gaps by examining Ca2+ channel-driven spontaneous burst firing in lateral olivocochlear (LOC) neurons, the most numerous auditory efferent neurons. Noise-induced hearing loss differentially affects Ca2+ channel subtypes by increasing high-voltage activated currents that further prolong burst firing and suggesting altered intracellular Ca2+ signaling. These significant changes in LOC firing behavior may profoundly impact their downstream targets in the cochlea.

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Hong, H., Trussell, L. O.. 2025-01-08. Noise-induced hearing loss enhances Ca2+-dependent spontaneous bursting activity in lateralcochlear efferents. https://doi.org/10.1101/2025.01.07.631771

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