University of Michigan
Novel mechanisms of cortical neuromodulation

Although there is currently no cure for tinnitus, recent experimental studies propose vagus nerve stimulation (VNS) may be a potential treatment to mitigate the condition because VNS releases natural chemicals (neuromodulators) that increase the brain’s ability to change. This is interesting because VNS has previously received Food and Drug Administration approval for treating drug-resistant epilepsy and treatment-resistant major depressive disorder. Despite considerable interest, how neuromodulators released by VNS could be therapeutically useful for tinnitus is unknown. This project will employ cutting-edge techniques to test a novel hypothesis: A major mechanism of action for neuromodulators is that they affect the function of dendrites, the long cable-like structures upon which neurons receive and integrate electrical signals. By identifying how neuromodulators impact the function of dendrites, these experiments may uncover novel targets for developing new treatments for tinnitus.

University at Buffalo, the State University of New York
Noise-induced tinnitus in mice

Animal models of tinnitus have employed many different behavioral techniques, only one of which is not subject to motivational issues and changes in auditory acuity. Tinnitus has previously been induced in rats following a sodium salicylate injection. In the present proposal, this paradigm will be modified to investigate tinnitus in mice. These experiments as a whole aim to determine the time course of tinnitus and its recovery following nontraumatic noise exposures in mice. Until there is an objective measure that separates hearing loss from tinnitus, it is difficult to use mice to study tinnitus. This project seeks to define a way to measure and characterize tinnitus in the awake and behaving mouse model in order to compare this to humans with tinnitus.

Massachusetts Eye and Ear, Harvard Medical School
Mechanisms and development of novel small molecule treatments for cochlear synaptopathy

Inner ear sensory hair cells detect sound vibrations in the inner ear and pass these signals to inner ear neurons, which ultimately send the signals to the brain. The synaptic connections between inner hair cells and neurons (nerve cells) can be lost from noise exposure, aging, or both. The loss of these connections results in what has been termed “hidden” hearing loss because it may be undetected via traditional auditory measures, and it may also be associated with other hearing disorders such as tinnitus and hyperacusis. To reestablish synaptic connections, we have developed a novel way to anchor special molecules that promote synaptic regeneration into the bone of the inner ear, to maximize the stimulation of inner ear neurons.

Johns Hopkins University

Modulation of neuro-glial cortical networks during tinnitus

My long term goals are to understand the complexity and temporal sequencing of tinnitus effectors with an integrative perspective, considering the interplay of the diverse cell types that might promote the development and maintenance of tinnitus to provide an updated interpretation of this disorder. Additionally, to use glial cells as a key therapeutic target to treat tinnitus.

Generously funded by the Les Paul Foundation

Oregon Health & Science University
Discovery of novel inhibitory cell types in the cochlear nucleus

Excessive neuronal electrical activity, or hyperactivity, is believed to underlie tinnitus. While many studies on hyperactivity have focused on a region called the dorsal cochlear nucleus, an auditory processing region in the brainstem, very little attention has been given to the ventral cochlear nucleus (VCN). This is surprising since the VCN is likely required for the activation of higher auditory centers in the brain. One likely cause of hyperexcitability is an imbalance between excitatory and inhibitory neuronal connections, or synapses. With the use of genetically modified mouse lines, we are able to reveal that the diversity of inhibitory cell types and circuitry within the VCN is far richer than previously described. Our primary goal is to discover and study the functional significance of these novel inhibitory neurons in the VCN whose inhibitory action, if compromised, could lead to hyperactivity and auditory dysfunction.

University of Pittsburgh
Characterizing tinnitus-induced changes in auditory corticofugal networks

The irrepressible perception of sounds without an external sound source is a symptom that is present in a number of different auditory dysfunctions. It is the primary complaint of tinnitus sufferers, who report significant “ringing” in the ears, and it is one of the primary sensory symptoms present in schizophrenia sufferers who “hear voices.” Tinnitus is thought to reflect a disorder in gain: A loss of input at the periphery shifts the balance of excitation and inhibition throughout the auditory hierarchy leading to excess hyperexcitability, which then leads to the perception of phantom sounds. This project aims to quantify how such “phantom sound” signals are routed and broadcast across the entire brain, and to understand how these signals impact our ability to perceive sound. Identifying improper regulation of brain-wide neural circuits in this way will provide a foundation for the development of new treatments for tinnitus and other hearing disorders.

University of Michigan
Development and transmission of the tinnitus neural code

Noise overexposure is a common risk factor of tinnitus, and is thus used as a common tinnitus inducer in animal research. However, noise exposure does not always cause tinnitus, and researchers would rely on behavioral testing to infer an animal’s subjective pathology. However, behavioral tests only work under the assumption that tinnitus is unchanging during the long testing period, which does not reflect the dynamic nature of tinnitus as well as ignoring variability. This inability to measure tinnitus within a short time window impedes our understanding of its emergence and progression. The project addresses these limitations through bypassing behavioral testing and directly identifying and locating an objective code for tinnitus in real-time spiking neurons. Using a novel data-driven approach, we can pinpoint exactly when/where tinnitus emerges and examine how noise trauma triggers and transmits the tinnitus signal throughout the auditory pathway.