Cortical mechanisms underlying aberrant auditory perception

University Of Rochester, Rochester NY

Investigators

Abstract

The present proposal will utilize an animal model and in vivo imaging techniques to determine whether altered cell-specific activity or disrupted neurotransmitter signaling in the auditory and frontal cortices underlie tinnitus and hyperacusis perception. Tinnitus (i.e., ringing in the ears) and hyperacusis (hypersensitivity to sound) are two highly prevalent and often debilitating auditory conditions. At present, the neural basis of these conditions remain unresolved, which has significantly hindered our ability to develop effective treatment strategies for ameliorating their perception. Prior studies suggest that tinnitus and hyperacusis may arise as a consequence of a maladaptive imbalance between excitation and inhibition in the auditory cortex following hearing loss. Additionally, top-down gating of this aberrant auditory activity by higher-level brain regions, such as the frontal cortex, has also been implicated as a contributing factor to tinnitus/hyperacusis perception. However, we currently lack an understanding of how altered activity of specific neuron sub-types and changes in neurotransmitter signaling within the auditory and frontal cortices differentially contribute to the generation of tinnitus, hyperacusis, or both conditions. The present proposal will use a validated operant conditioning tinnitus behavioral paradigm co-developed by the PI and a sound-avoidance hyperacusis task, combined with advanced in vivo imaging techniques to advance our understanding of the neural basis for these auditory conditions. Using cell-specific calcium imaging via miniscopes, Aim 1 will investigate the contribution of altered pyramidal cell activity in the auditory and frontal cortices to tinnitus/hyperacusis perception. In Aim 2, fiber photometry recordings of neurotransmitter signaling in the auditory and frontal cortices will be used to determine whether altered glutamatergic/GABAergic signaling underlie perception of these auditory conditions. Ultimately, results from these experiments are expected to have high impact because they will identify potential cell-specific and neurotransmitter-specific therapeutic targets for treating tinnitus and hyperacusis perception. Dr. Sarah Hayes, Au.D., Ph.D. is a clinician-scientist dedicated to providing audiological care for patients with tinnitus and hyperacusis, and advancing our understanding of the neural basis for these disorders through her research. This proposal leverages her extensive experience in animal behavioral assessments of auditory disorders and electrophysiological recordings in rodents, to provide her with the opportunity to develop new skills in advanced in vivo imaging techniques, while moving the field forward in elucidating the neural basis for tinnitus/hyperacusis. Additionally, the technical expertise that she will acquire through this proposal will help establish a scientific platform for her to identify and assess therapeutic targets and treatments for tinnitus and hyperacusis. Collectively, the expertise of her mentorship/advisory team, combined with the vibrant collective of hearing, balance, and neuroscience researchers at the University of Rochester provides an ideal setting for Dr. Hayes to develop into a successfully funded independent investigator.