The transcriptomic state of spiral ganglion neurons across different hearing loss models

In the inner ear, spiral ganglion neurons (SGNs) are essential for transmitting sound information to the brain. Morphological, electrophysiological and transcriptomic characterisation subdivides them into two types: type I SGNs contact the inner hair cells that transduce and transmit sound information, while type II SGNs contact outer hair cells that have a critical role in sound amplification and tuning. Type I SGNs are further subdivided into types Ia, Ib, and Ic. The success of any therapeutic intervention aimed at recovering, enhancing or replacing auditory function rests on the presence of healthy and functional SGNs. To this end, general approaches like anti-inflammatory drugs are routinely used in the clinic, but these do not directly target SGNs. The aim of this PhD project is to study how each subtype of SGN is affected by acute or chronic hearing loss and identify targets to potentially mitigate their indirect damage and improve their function. To study their transcriptomic state at the single cell level, single nuclei RNA sequencing of dissected mouse spiral ganglia will be performed using combinatorial barcoding, profiling ~100,000 nuclei across three well-established mouse models of hearing loss: congenital hearing loss (Otof knock mouse), aminoglycoside-induced hair cell damage and noise-induced hearing loss. The comparison of the transcriptomic states of types and subtypes of SGNs within and across these different models of hearing loss will allow the identification of novel genes, signalling pathways or biological processes to be directly targeted at the clinic.