Sensory regions of the adult cerebral cortex retain a remarkable plasticity that supports large-scale reorganization following peripheral nerve injury. In the auditory system, degeneration of the afferent pathway that transmits acoustic information from the cochlea to the brain can have only minor effects on pure tone audibility, yet greatly disrupts perceptual discrimination of complex, temporally modulated sounds, such as speech in noise. While this dichotomous perceptual outcome is normally attributed to the number and properties of surviving auditory nerve fibers, we propose that compensatory plasticity at higher levels of the central auditory pathway also plays a critical role in preserving the discriminabilit of rudimentary sounds. To address this hypothesis, we propose to study the loss and partial recovery of auditory system function - from cochlea to the cortex - in adult mice treated with ouabain, a Na+/K+ ATPase inhibitor that lesions afferent fibers in the auditory nerve but leaves the cochlear sound transduction machinery intact. Studies in Aim 1 test the hypothesis that near-complete elimination of Type-I spiral ganglion neuron (SGN) synapses onto inner hair cells will eliminate temporal gap detection behavior, acoustic reflexes, and the auditory brainstem response (ABR), yet behavioral tone detection thresholds will rapidly recover to within normal limits. Studies in Aim 2 will address the hypothesis that the preservation of behavioral hearing thresholds is linked to a compensatory neuronal plasticity that occurs downstream of the brainstem generators of the ABR and acoustic reflexes. By simultaneously tracking ensembles of units in the auditory cortex and inferior colliculus before and after cochlear denervation, studies in Aim 2 seek to show that compensatory plasticity improves the sensitivity and dynamic range of sound properties that are effectively encoded by overall spike rate, but offers little benefit to sound properties encoded by precise action potential timing. By tracking behavioral discrimination of the same sound features used for neurophysiological testing, we will be able to determine whether and how homeostatic plasticity in cortical and midbrain ensembles relates to changes in perceptual acuity. Whereas studies in Aims 1 and 2 focus on reorganization following unilateral cochlear denervation, experiments in Aim 3 will study mice with bilateral ouabain treatment to address the hypothesis that an even more complete recovery of rate-based coding and perceptual discrimination abilities can be achieved when SGN degeneration is matched, rather than imbalanced. Collectively, these studies will address basic science questions related to the hierarchical plasticity of rate versus temporal coding strategies and will identify a fundamental role for compensatory gain control at higher levels in the CNS in the perceptual sequelae of primary auditory neuropathy.
Hidden hearing loss describes a condition where sound detection thresholds are relatively normal but individuals struggle to discriminate complex sounds, such as speech, particularly in noisy background environments. Hidden hearing loss may arise from degeneration of the auditory nerve without accompanying cochlear pathology, as is known to occur as a normal process of aging, after intense noise exposure, or in individuals diagnosed on the auditory neuropathy spectrum. This proposal seeks to understand the contribution of brain plasticity to the preservation of rudimentary sound awareness following profound degeneration of the auditory nerve. This work will shed additional light on the neurobiological underpinnings of hidden hearing loss and suggest new therapeutic approaches.
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