< Program

Special Session: Uncovering Hidden Hearing Loss: Noise Exposure, Tinnitus and Aging

Cochlear Deafferentation in Noise-Induced and Age-Related Hearing Loss
Sharon G. Kujawa, PhD, Professor of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA

OBJECTIVES: Insights from animal studies suggest that synaptic connections between cochlear inner hair cells and primary afferent neurons are among the cellular elements most vulnerable to noise and aging, two primary etiologies of acquired sensorineural hearing loss in humans. Based on the synthesis of research threads from studies conducted in animal models, human temporal bones and living humans with and without audiometrically-defined hearing loss, we are pursuing a set of physiological, psychophysical and behavioral assays of cochlear function, with linked histopathology, to identify and characterize effects of cochlear synaptopathy/deafferentation on threshold and suprathreshold hearing. Providing key background observations and recent updates of findings, this talk will review basic findings of altered structure and function in animal models, with implications for diagnosis and treatment.  

DESIGN: Cochlear physiologic and histologic consequences of noise exposure and aging have been assessed in multiple species. As a general strategy, noise exposures are titrated to produce varying levels of cochlear synaptopathy, with and without permanent threshold elevations and hair cell injury, compared to age and sex-matched controls. For aging studies, animals are held to various log-spaced ages over the nominal life span relevant to the species under study, with corresponding characterizations of structure and function. 

RESULTS: Between 2009 and 2013, published studies in noise-exposed and aging mice from our labs showed that synapses between auditory nerve fibers and inner hair cells disappear even after noise exposures that cause only transient threshold shifts or, in aging ears, before either outer hair cell loss or the resultant threshold shifts first appear. In subsequent years, the phenomenon of noise-induced or age-related primary cochlear deafferentation was documented in multiple mammalian species, including humans. It was exaggerated in aging ears with recovered thresholds after prior noise exposure. The deafferentation, whether created by surgical nerve section, acoustic overexposure or ototoxic drugs, does not raise electrophysiological or behavioral thresholds until it is nearly total. Single unit electrophysiology and novel round window recorded responses suggest different noise-dose and age-sensitive vulnerabilities of auditory nerve fibers by spontaneous rate subtype.

CONCLUSIONS: Declines in neural activity and histologic evidence of synapse loss revealed in these studies are consistent with noise-dose and age-sensitive pathophysiology and histopathology. Results will inform our understanding of the declines in function underlying injury, aiding efforts toward improved clinical diagnosis and treatment.

Work presented has been supported by grants from the NIH/NIDCD, the Office of Naval Research and the Department of Defense. 

Sharon G. Kujawa, PhD is a Professor of Otolaryngology-HNS at Harvard Medical School and holds the Sheldon and Dorothea Buckler Chair in Otolaryngology at Massachusetts Eye and Ear, where she is the Director of Audiology Research in the Department of Otolaryngology and a Senior Scientist in the Eaton-Peabody Laboratories. Dr. Kujawa is a clinician and an auditory neuroscientist whose research seeks to clarify mechanisms and functional consequences of common causes of acquired sensorineural hearing loss, most recently focused on the cochlear synaptopathy underlying noise-induced and age-related hearing loss, and to translate that knowledge into improved diagnosis and treatments.