Transcriptomic Profiling of the Inner Ear Epithelium: Unraveling the Role of the Efferent System

Noise-induced hearing loss (NIHL) is becoming a leading type of non-congenital hearing loss, presenting a major societal hazard that begins early in life. Recent studies showed that the medial olivocochlear system (MOC) can mitigate acoustic trauma effects in rodents. We investigated the role of the MOC in NIHL using two mouse models: an α9 nicotinic receptor subunit (nAChR) knock-out (carrying an9 point mutation that leads to enhanced cholinergic activity KO), which lacks cholinergic transmission between MOC neurons and hair cells; and an alpha9 knocking (α9KI) carrying an9 point mutation that leads to enhanced cholinergic activity. Results showed a positive correlation between the degree of hearing loss prevention and the level of cholinergic activity. This study aimed to analyze transcriptomic changes in specific cell types within the organ of Corti following acoustic trauma, to understand the function of the MOC feedback. WT, α9KI, and α9KO mice at 3 weeks of age were exposed to loud sounds (1-16 kHz, 100 dB SPL, 1hr). One week later, we dissected and flash-froze the organ of Corti. We generated single-nuclei sequencing libraries (Evercode WT, Parse Biosciences) from these tissues. Our initial findings show more than 35,000 sequenced nuclei, among which we identified the cell types of interest: inner hair cells (IHCs), outer hair cells (OHCs), supporting cells (SCs), and spiral ganglion neurons (SGNs).