Enhancement of MOC activity prevents the onset of hidden hearing loss after acoustic trauma

BOERO L; ELGOYHEN AB; GOUTMAN J; CASTAGNA V; GOMEZ CASATI ME

Congreso; XIII Reunión Anual de la Sociedad Chilena de Neurociencia 2017; 2017

Noise induced hearing loss (NIHL) is growing as one of the most prevalent types of non-congenital hearing loss. It has been proposed that activity of the medial olivocochlear system (MOC) can ameliorate acoustic trauma effects. To address the role of the MOC in NIHL, we used two different mouse models: an alpha9 knock-in (KI), in which the alpha9 nicotinic cholinergic receptor (nAChR) subunit bears a mutation and leads to enhanced MOC activity; and also, one lacking the alpha9 subunit (KO). We exposed WT, KI and KO mice at 3 weeks of age to loud sounds and tested their cochlear function 1 and 7 days after exposure. Large auditory threshold shifts were found one day after exposure in WT and KO mice, whereas KI mice were resistant to the same protocol. One week later, thresholds returned to normal in WT but KO ears did not recover. Permanent reduction in auditory brainstem responses peak I amplitudes were found in WT and KO mice after exposure reflecting an ongoing process of hidden hearing loss. Notably, KI mice did not suffered any changes after acoustic overexposure. Synaptophysin immunostaining evidenced a reduction of efferent terminals contacting outer hair cells (OHCs) at 7 days after trauma in WT mice. KO mice showed a distribution of efferent innervation shifted to minor contacts per OHC, whereas KI mice presented a wider innervation pattern and centered in 3-4 contacts per OHC. Finally, whole mount immunostaining for pre-synaptic ribbons and post-synaptic AMPA-receptor were performed to assess the degree of de-afferentation in inner hair cells (IHCs) followed by acoustic overexposure. Traumatized WT mice showed a reduction in the number of ribbons and afferent terminals that was only significant at the apical turn. KO mice showed a decrease in the number of synaptic puncta mostly at middle and high frequencies after acoustic trauma. Interestingly, KI mice developed an increase in the number of synapses after acoustic trauma. Results obtained show that enhancement of MOC reflex can prevent the appearance of hidden hearing loss as a consequence of noise exposure. Additionally, immunohistochemical data suggests that the MOC system is a key player on the balance between synapse formation and degeneration after exposure to loud noise in the inner ear.