ESTABLISHING A GENETIC MOUSE MODEL OF UNILATERAL HEARING RESTORATION

Mounting evidence shows that congenital single-sided deafness impairs binaural cues, speech perception, and language acquisition. Therapeutic approaches, including unilateral cochlear implantation, do not fully restore these functions and the mechanisms underlying this imbalance remain unknown. Patient imaging and electrophysiology data reveal asymmetric activation patterns between the auditory cortices of unilateral implant users, with hemispheric activation asymmetries persisting even years after initial implantation. These asymmetries in activation correlate with poorer speech perception outcomes, likely due to plasticity changes from uneven cochlear input. Similar distortions appear in animal models of monaural deprivation, including disrupted tonotopy and weakened binaural integration. Many animal models of hearing restoration in single-sided deafness mainly rely on obstructing the auditory canal, causing in most cases only partial monaural deprivation. A controllable genetic model of reversible single-sided deafness would thus be beneficial to decipher how unilateral and bilateral hearing restoration differentially alter cortical circuits after defined deafness durations. Here, we established a genetic mouse model of hearing restoration following deafness paired with cochlear trauma via injection into the round window. This methodology generates cohorts with left-ear, right-ear, or bilateral hearing restoration at chosen postnatal ages, enabling exact control over hearing recovery onset, side, and duration. This model provides a platform for detailed molecular and functional studies of unilateral and bilateral hearing restoration, revealing the circuit features that give rise to asymmetries in auditory processing.