Translational Research IIIAuditory Olivocochlear Efferent Feedback System Changes with Aging and Noise Exposure Objectives: The role of the medial olivocochlear system in perception has been debated by psychophysicists for many years due to conflicting and variable results in human and animal studies, often violating hypotheses that are based on well-characterized physiological anti-noise masking mechanisms in the auditory nerve. Studies in lesioned animals also produced mixed perceptual outcomes, sometimes showing recovery of performance with continued practice. The emergence of genetically engineered mouse models has provided new opportunities for the investigation of increased or decreased olivocochlear activation in intact animals that can be tested across the lifespan under controlled experiential conditions. We can also study the effects of noise and age in these models housed under controlled acoustic conditions. Design: We use a variety of conditioned and reflexive behavioral assays, non-invasive physiological tests, and quantitative anatomical analysis techniques to investigate how genetic manipulations of the olivocochlear system affect hearing outcomes in young, middle aged, and old mouse models exposed to varying acoustic conditions. Results: In this talk, I will summarize our findings obtained over the years from various controlled mouse models. One might expect mouse models to yield more clear-cut behavioral disruptions, but these animals do not always perform as expected on behavioral sound detection and discrimination tasks. In contrast, acoustic startle reflex-based and evoked potential measurements have identified several functional effects of diminished or enhanced olivocochlear activity, including abnormal reactivity to loud sounds and temporal processing deficits. Newer techniques such as optogenetics and gene therapy show promise for revealing the specific effects of acute olivocochlear activation or deactivation provided that appropriate controls are implemented. Conclusions: Contributions of the ascending peripheral and central auditory pathways to age-related and noise-induced hearing deficits have been well-characterized, but we know comparatively little about how the descending projections from the brain to the cochlea contribute to hearing deficits. Early-life deficits observed in mouse models with deficient olivocochlear function may reflect abnormal central auditory system development rather than overt peripheral olivocochlear modulation of afferent activity. Diminished olivocochlear efferent function appears to be most detrimental to hearing in aged and aged, noise-exposed auditory systems which are already working with reduced afferent input to the brain. However, plasticity in remaining neurons in this system may compensate for some aspects of this decline and may explain the variable behavioral outcomes reported in animals and humans.
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