The role of auditory nerve activity in noise-induced tinnitus

• Applicant: Dr. Amarins Heeringa
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499193277

The past few decades have seen numerous studies on the pathophysiology of tinnitus in the central auditory system. Neurons of the central auditory pathway have been probed for aberrant spontaneous and stimulus-evoked activity in animals with behavioural evidence of tinnitus. These recordings, and other types of data, have given rise to several overarching theories explaining phantom sound perception. In most of these theories, peripheral cochlear damage initiates the tinnitus-related changes in the central system. Indeed, tinnitus is strongly correlated to a history of noise exposure and to an abnormal audiogram. The auditory nerve connects the cochlea to the central auditory system. If cochlear damage is to effect central changes, activity of single auditory-nerve fibres should also be affected. In noise-induced tinnitus, it is unknown whether tinnitus-specific changes first occur in the peripheral auditory system, or rather more centrally. Therefore, I am proposing to record spontaneous activity from single auditory-nerve fibres of noise-exposed animals with and without behavioural evidence of tinnitus. As such, general effects of noise exposure can be disentangled from tinnitus-specific changes. We know that the effects of noise exposure on central pathophysiology are not static, but rather dynamic in time, especially within the first days and weeks after the exposure. Therefore, I propose to carry out this experiment in two different cohorts of animals, recording auditory-nerve activity at 3 days and 3 weeks following noise exposure and tinnitus assessment. As of yet, recovery after recording single-unit auditory nerve activity is not possible. Therefore, in humans, wave-I of the auditory brainstem response (ABR) is commonly used to assess physiological properties of the auditory nerve. It has been shown that the latency of the ABR wave-I is delayed with tinnitus. However, such a latency shift can be caused by multiple pathologies, such as a reduced number of available fibres or a shift in response latency of single fibres. Therefore, responses of single auditory fibres to ABR stimuli will also be recorded in the above-described experiments. By combining compound and single-unit data from the same animals, some of the underlying mechanisms that cause putative tinnitus-related changes in wave-I morphology can be disentangled. Knowledge gained from this project will help interpret the large body of research on tinnitus-related changes in the central auditory pathway, resolving issues regarding the link between tinnitus and peripheral cochlear damage.

• DFG Programme: Research Grants