RT Journal Article
SR Electronic
T1 Enhancement of the medial olivocochlear system prevents hidden hearing loss
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 0363-18
DO 10.1523/JNEUROSCI.0363-18.2018
A1 Boero, Luis E.
A1 Castagna, Valeria C.
A1 Di Guilmi, Mariano N.
A1 Goutman, Juan D.
A1 Belén Elgoyhen, Ana
A1 Gómez-Casati, María Eugenia
YR 2018
UL http://www.jneurosci.org/content/early/2018/07/20/JNEUROSCI.0363-18.2018.abstract
AB Cochlear synaptopathy produced by exposure to noise levels which only cause transient auditory threshold elevations is a condition that affects many people and is believed to contribute to poor speech discrimination in noisy environments. These functional deficits in hearing, without changes in sensitivity, have been called hidden hearing loss (HHL). It has been proposed that activity of the medial olivocochlear (MOC) system can ameliorate acoustic trauma effects. Here we explore the role of the MOC system in HHL by comparing the performance of two different mouse models: an α9 nicotinic receptor subunit knock-out (Chrna9 KO) which lacks cholinergic transmission between efferent neurons and hair cells, and a gain of function knock-in (Chrna9L9′T KI) carrying an α9 point mutation that leads to enhanced cholinergic activity. Animals of either sex were exposed to sound pressure levels that in wild-type (WT) produced transient cochlear threshold shifts and a decrease in neural response amplitudes, together with the loss of ribbon synapses, indicative of cochlear synaptopathy. Moreover, a reduction in the number of efferent contacts to OHCs was observed. In Chrna9 KO ears, noise exposure produced permanent auditory threshold elevations together with cochlear synaptopathy. 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.SIGNIFICANCE STATEMENTNoise overexposure is a major cause of a variety of perceptual disabilities, including speech-in-noise difficulties, tinnitus and hyperacusis. Here we show that exposure to noise levels that do not cause permanent threshold elevations nor hair cell death, can produce a loss of cochlear nerve synapses to inner hair cells (IHCs) as well as degeneration of MOC terminals contacting the outer hair cells (OHCs). Enhancement of the MOC reflex can prevent both types of neuropathy, highlighting the potential use of drugs that increase α9α10 nicotinic cholinergic receptor activity as a pharmacotherapeutic strategy to avoid HHL.