Cochlear synaptopathy and neurodegeneration in noise and aging: Peripheral contributions to auditory dysfunction with normal thresholds

Abstract

Declining auditory performance in listeners with normal audiometric thresholds is often attributed to changes in central circuits, based on the widespread view that normal thresholds indicate a lack of cochlear involvement. Recent work in animal models of noise and aging, however, demonstrates that there can be functionally important loss of sensory inner hair cell—afferent fiber communications that go undetected by conventional threshold metrics. We have described a progressive cochlear synaptopathy that leads to proportional neural loss with age, well before loss of hair cells or age-related changes in threshold sensitivity. Similar synaptic and neural losses occur after noise, even when thresholds return to normal. Since the IHC-afferent fiber synapse is the primary conduit for information to flow from the cochlea to the brain, and since each of these cochlear nerve fibers makes synaptic contact with one inner hair cell only, these losses should have significant perceptual consequences, even if thresholds are preserved. The prevalence of such pathology in the human is likely to be high, underscoring the importance of considering peripheral status when studying central contributions to auditory performance declines. [Research supported by R01 DC 008577 and P30 DC 05029.]