Enhancement of the medial olivocochlear system prevents hidden hearing loss

BOERO, L; CASTAGNA, V; GOUTMAN, JD; ELGOYHEN, AB; GOMEZ CASATI, ME

San Diego

Congreso; Society for Neuroscience; 2018

Hearing loss is a major public health problem, given that its impact on human communication and quality of life is devastating. Noise exposure has gained relevance as one of the most important sources, although the underlying causes of noise-induced hearing loss are still unknown. Recently, it has been demonstrated that acoustic trauma (AT) producing only transient auditory threshold shifts also produces long-term structural damages to the inner ear, such as a reduction in the number synapses between inner hair cells (IHCs) and afferent neurons. This has been called hidden hearing loss (HHL) because it is not apparent in an audiogram. Medial olivocochlear (MOC) efferent neurons form a negative feedback gain-control system that inhibits amplification of sounds by the action of acetylcholine on a9a10 cholinergic nicotinic receptors at the base of outer hair cells (OHCs). It has been proposed that activity of the MOC fibers can ameliorate AT effects.Here we explore the role of the MOC system in HHL by comparing the performance of two different mouse models after AT: an a9 nicotinic receptor subunit knock-out (Chrna9 KO) which lacks cholinergic transmission between efferent neurons and OHCs, and a gain of function knock-in (Chrna9L9?T KI) bearing an a9 point mutation that leads to enhanced MOC activity. Animals of either sex were exposed to 1-16 kHz noise of 100 dB SPL for 1 hour. This sound pressure levels produced in WT mice transient auditory brainstem responses (ABRs) threshold shifts, a decrease in neural response amplitudes and loss of ribbon synapses, indicative of cochlear synaptopathy. In Chrna9 KO ears, we also found cochlear synaptopathy but the ABR threshold shifts were permanent. In contrast, the Chrna9L9?T KI was completely resistant to the same acoustic exposure protocol. These results show a positive correlation between the degree of HHL prevention and the level of cholinergic activity. Notably, enhancement of the MOC feedback promoted new afferent synapse formation, suggesting that it can trigger cellular and molecular mechanisms to protect and/or repair the inner ear sensory epithelium.Additionally, we were interested in elucidating if AT could affect the capacity of IHCs to release glutamate. Patch-clamp recordings were performed on IHCs in an ex-vivo cochlear preparation of exposed and control mice. Glutamate release from IHCs was estimated by monitoring cell membrane capacitance with a lock-in amplifier. We found an increase in capacitance changes and Ca2+ currents in noise exposed animals. These results suggest presynaptic overcompensation after acoustic overexposure.