The magnitude of acoustic injury to the ear is inversely correlated with alpha9alpha10 nAChR activity.

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

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

Noise induced hearing loss (NIHL) is growing as one of the most prevalent types of non-congenital hearing loss. It has become a major hazard in society and begins early in life. Recently, it has been proposed that activity of the medial olivocochlear system (MOC) can ameliorate acoustic trauma effects in rodents. In order to address the role of the MOC in NIHL, we made use of a mouse model in which the alpha9 nicotinic cholinergic receptor (nAChR) subunit bears a mutation and leads to enhanced MOC activity (Chrna9L9?T knock-in (KI)), in addition to one lacking the alpha9 subunit of the nicotinic receptor (Chrna9 knockout (KO)). We exposed WT, KI and KO mice at 3 weeks of age to loud sounds (1-16 kHz, 100 dB SPL, 1hr) 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 noise exposure. One week later thresholds returned to normal in WT but KO ears did not recover. Synapthophysin immunostaining evidenced a reduction of efferent terminals contacting outer hair cells at 7 days after trauma in WT mice. Cochlear ribbon synapses to inner hair cells, visualized through whole mount immunostaining for pre-synaptic ribbons (CtBP2) and post-synaptic AMPA-receptor patches (GluA2) revealed a significant reduction in the number of synapses in KO and WT mice 7 days after acoustic trauma, while they were not modified in the KI. Results obtained suggest that the degree of protection from acoustic injury depends on the level of MOC activity. Most importantly, despite complete recovery of cochlear thresholds, exposure to loud noise can cause irreversible changes on the innervation pattern to the inner ear.