Enhancement of the medial olivocochlear system prevents hidden hearing loss

BOERO, LUIS E.; CASTAGNA, VALERIA C.; DI GUILMI, MARIANO N.; GOUTMAN, JUAN D.; BELÉN ELGOYHEN, ANA; GÓMEZ-CASATI, MARÍA EUGENIA

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2018 vol. 38 p. 7440 - 7451

0270-6474

Cochlear synaptopathy produced by exposure to noise levels that cause only transient auditory threshold elevations is a condition thataffects many people and is believed to contribute to poor speech discrimination in noisy environments. These functional deficits inhearing, without changes in sensitivity, have been called hidden hearing loss (HHL). It has been proposed that activity of the medialolivocochlear (MOC) system can ameliorate acoustictrauma effects. Here we explorethe role ofthe MOC system in HHL by comparingtheperformance of two different mouse models: an 9 nicotinic receptor subunit knock-out (KO; Chrna9 KO), which lacks cholinergictransmission between efferent neurons and hair cells; and a gain-of-function knock-in (KI; Chrna9L9T KI) carrying an 9 point mutationthat leads to enhanced cholinergic activity. Animals of either sex were exposed to sound pressure levels that in wild-type producedtransient cochlear threshold shifts and a decrease in neural response amplitudes, together with the loss of ribbon synapses, which isindicative of cochlear synaptopathy. Moreover, a reduction in the number of efferent contacts to outer hair cells was observed. In Chrna9KO ears, noise exposure produced permanent auditory threshold elevations together with cochlear synaptopathy. In contrast, theChrna9L9T KI was completely resistant to the same acoustic exposure protocol. These results show a positive correlation between thedegree of HHL prevention and the level of cholinergic activity. Notably, enhancement of the MOC feedback promoted new afferentsynapse formation, suggesting that it can trigger cellular and molecular mechanisms to protect and/or repair the inner ear sensoryepithelium