The magnitude of acoustic injury to the ear is inversely correlated with α9α10 nAChR activity."

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

Congreso; 39th Midwinter Meeting, Association for Research in Otolaryngology; 2016

Noise induced hearing loss (NIHL) has become a major public health problem. The protectiverole of the medial olivocochlear system (MOC) in NIHL has been well documented (Kujawa andLiberman, 1997; Taranda et al., 2009). Here, we explore the effects of acoustic overstimulationon the efferent innervation to the cochlea and analyze these changes in mice with differentdegrees of efferent feedback. For this purpose, we made use of a mouse model in which the α9nicotinic receptor subunit bears a mutation and leads to enhanced MOC activity (Chrna9L9?Tknock-in (KI)) in addition to one lacking the α9 subunit of the nicotinic receptor (Chrna9knockout (KO)).We exposed WT, KI and KO mice to loud sounds (1-16 kHz noise at 100 dB, for 1 h.) at 3weeks of age and tested at 1 and 7 days after the exposure. Auditory brainstem responses(ABR) and distortion product otoacoustic emissions (DPOAEs) were used to verify cochlearfunction. Olivocohlear terminals to outer hair cells (OHC) were quantified by whole mountimmunostaining for synaptophysin, an integral protein of the synaptic vesicle membrane toreveal the overall efferent innervation.We found large auditory threshold shifts one day after exposure in WT and KO mice (10-30 dBSPL). However, one week later, thresholds returned to normal in WT, whereas the KO ears didnot recover. Synaptophysin immunostaining revealed abnormalities in efferent terminal numberafter acoustic trauma in WT mice. The number of terminals per OHC before exposure rangedfrom 1 to 5, with most OHC contacted by 2 and 3 terminals (40 and 42%, respectively). Afteracoustic trauma, most OHC were contacted by only 1 or 2 terminals (38 and 44%, respectively)and very few by more than two. Notably, the innervation pattern of KO mice before acoustictrauma is similar to the one observed in WT mice post-trauma, and it does not change afterexposure to loud sounds. In contrast, auditory thresholds of KI displayed no changes after noiseexposure. Additionally, Chrna9L9?T point mutation showed an increase in the number ofterminals per OHC and as many as 7 terminals on some OHC. Interestingly, this innervationpattern was not altered by exposure to loud noise.Results obtained suggest that the degree of protection from acoustic injury depends on the levelof MOC activity. Most importantly, despite complete recovery of cochlear thresholds, exposureto loud noise can cause irreversible changes on the efferent innervation pattern to the inner ear.