PROBING THE REVERSIBILITY OF CENTRAL AUDITORY CIRCUITS USING A NEW GENETIC MODEL OF HEARING RESTORATION

Studies of genetic forms of deafness have provided key insights into the development, functioning and pathophysiology of the cochlea, the mammalian auditory sensory organ. Despite these advances, complete hearing restoration after deafness resulting in hearing capabilities comparable to those of a normally hearing individual has not yet been achieved. Auditory deprivation during youth progressively leads to irreversible peripheral and central auditory deficits that worsen with the severity and duration of hearing impairment. To gain insight into the mechanisms accounting for the irreversibility of these hearing loss-related deficits, we developed a new genetic mouse model of hearing restoration. This conditional genetic mouse line provides an ideal and reproducible model to investigate how the timing of auditory restoration shapes recovery of the auditory system and the pathophysiological mechanisms preventing the reversibility of central auditory deficits. Here, the neuronal activity in control hearing mice and hearing restored mice following a period of congenital deafness is compared along the auditory pathways using high-density electrophysiological recordings. Restoration of auditory function was probed at multiple levels along the central auditory pathway, including the cochlear nucleus, the inferior colliculus and the primary auditory cortex, to investigate the potential irreversibility of central auditory deficits following deafness. To delve into cellular functional details, we developed a new pipeline to track the neuronal cell types based on their electrophysiology signature. Understanding the functional behavior of auditory neurons and their sensitivity after temporary deafness may enable the development of new therapeutic strategies to improve recovery from central auditory deficits.