Project 1:Investigations into Residual Function Following Unilateral Hearing Loss

Project Summary Hearing loss can be a congenital or acquired condition, either a conductive or a sensorineural variety of loss and bilateral or unilateral. Unilateral hearing loss is the more common condition. Congenital unilateral hearing loss occurs in 1 out of 1,000 births. Unilateral conductive hearing of all etiologies occurs in ~30 million adults. Importantly, balance impairment and unilateral hearing loss are often comorbidities, increasing fall risk and associated hospitalization and death of the aging population. However, unilateral hearing loss and its effects on residual hearing and balance, is relatively understudied. When investigated, results have often not been in agreement between studies, perhaps generated by differences in experimental protocols employed. Thus, significant gaps in knowledge exist regarding whether: 1) neural processing in the contralesional inner ear, most often assumed to be normal, is actually physiologically compromised: 2) whether different modes of loss (full sensorineural versus conductive (partial) loss) result in different outcomes for the contralateral end organs; and 3) whether either full sensorineural or conductive hearing loss induces synaptic plasticity events along the auditory and /or vestibular central pathways that could potentially result in dysfunctional processing, sensory mapping, etc. Such data will be important for future investigations into whether there exists drug targets whose manipulation might affect a better hearing/balance outcome. We will pursue three main aims to investigate these issues. In Aim 1 we will test the hypothesis that unilateral sensorineural hearing loss and conductive hearing loss alter the physiology of the remaining intact inner ear(s). We will assess physiology (ABRs and single fiber electrophysiology) of the remaining cochlea following induction of both varieties of hearing loss. Further, we will evaluate vestibular function by recording vestibulo-ocular reflexes in mice with conductive hearing loss. In Aim 2, we will test the hypothesis that unilateral sensorineural hearing loss and conductive hearing loss induce inflammation in the remaining intact inner ear, suggesting mechanisms by which pathophysiological outcomes occur. Finally, in Aim 3 we will test the hypothesis that unilateral sensorineural hearing loss and conductive hearing loss alter synaptic plasticity within target nuclei along the central auditory and vestibular pathways. We will examine known contributors to both physiological and structural plasticity. At the conclusion of these studies, we will have more completely defined the effects of unilateral inner ear dysfunction on residual hearing and vestibular systems. Such data will be important for future strategies designed to help patients with this common condition.