Noise-induced hearing loss enhances Ca2+-dependent electrical activity in lateral cochlear efferents.

Abstract

Exposure to loud and/or prolonged noise damages cochlea and triggers downstream brain changes, resulting in hearing loss and altered speech comprehension. It remains unclear however whether noise exposure also compromises the cochlear efferent system, a feedback pathway originates in the brain that fine-tunes hearing sensitivity in the cochlea. Recent evidence suggests that lateral olivocochlear (LOC) efferent system supports hearing recovery by sustaining auditory nerve activity for several weeks after acoustic trauma (Sitko et al., 2025); however, the underlying neural mechanisms have not been fully elucidated. To address this gap, we examined the long-term effects of noise-induced hearing loss on the spontaneous action potential (AP) firing pattern in mouse LOC neurons of either sex. Under normal conditions, these neurons display a characteristic burst firing pattern driven by Ca²⁺ channel-mediated membrane voltage oscillations. One week following noise exposure, hearing thresholds were significantly elevated, and the duration of AP bursts was increased, as a result of an enhanced Ca²⁺ current. Moreover, LOC neurons exhibit Ca²⁺-dependent inactivation (CDI) of Ca²⁺ currents - a key process that shapes the duration of voltage oscillations - whose properties were also modified following noise exposure. Interestingly, our data suggest that the interplay between Ca²⁺ channel activation, CDI, and outward leak currents is sufficient to sustain the oscillating behavior of LOC neurons. We propose that noise-induced hearing loss increases efferent activity, thereby enhancing the release of neurotransmitters and neuropeptides, which may support long-lasting restoration of sensory coding in the damaged cochlea.Significance Statement while noise-induced hearing loss has been extensively studied in the auditory afferent system, its effects on the efferent system, a key modulator of hearing sensitivity, remain poorly understood. This study addresses this gap by examining Ca²⁺ channel-driven spontaneous burst firing in lateral olivocochlear (LOC) neurons, the most numerous auditory efferent neurons. We find that noise exposure selectively increases high-voltage activated Ca²⁺ currents, prolonging burst duration and potentially altering intracellular Ca²⁺ signaling. These changes persist for more than a week and may significantly affect LOC output to the cochlea. Given the role of Ca²⁺ channels in many neurological diseases, this study highlights their underexplored relevance in auditory disorders and the long-term impact of efferent system plasticity on hearing.