By Tenzin Ngodup, Ph.D.
Tinnitus is the perception of a phantom sound, commonly known as “ringing in the ears.” It is a highly prevalent condition and in some cases, can significantly impair the quality of life. Unfortunately, the underlying causes of tinnitus are unknown. However, animal and human studies have linked tinnitus with hyperactivity of auditory neurons in the brain.
Specifically, recent studies implicated hyperactivity in the ventral cochlear nucleus (VCN) as a possible source of tinnitus generation. The VCN is one of the first brain structures to receive auditory information from the ears, and electrical activity in the VCN leads to activity in higher auditory centers. Therefore, an increase in the excitability of neurons in the VCN could lead to higher excitability of neurons observed in higher auditory centers.
Reconstruction of the structure of both D-stellate (A) and novel L-stellate (B) cells. D-stellate cells show radiated structures while L-stellate cells show profusely branched processes.
This early-level activity of excitatory neurons is regulated by inhibitory neurons. Since inhibitory neurons act to prevent hyperactivity, it is logical to look to them as we examine normal and damaged auditory function, but the sources of these inhibitory inputs onto the excitatory cells in VCN are not well understood.
Within the VCN, the activity of excitatory neurons is regulated by a single known inhibitory cell class, called the D-stellate cell. The goal of this study was to take a closer look at the VCN, which may reveal new types of inhibitory neurons with functions that could be of clinical significance. By carefully examining the diversity of inhibitory neurons in the VCN using transgenic mice, super-resolution microscopy, and the latest tools to study the structure and properties of individual neurons, we discovered a novel class of inhibitory cell, which we termed L-stellate cells in the VCN. Our study published in eLife in November 2020 described this novel inhibitory cell class.
We were surprised to find that the vast majority of inhibitory neurons in the VCN are this L-stellate cells class, as compared with the better-known D-stellate cells. The L-stellate cells differ from D-stellate cells both in structure and physiological properties. We also showed that the L-stellate cells provide inhibitory signals to excitatory cells in the VCN—that is, they reduce the electrical activity.
This is an exciting and significant finding because the balance of excitation and inhibition is critical for normal cell activity. The disruption of inhibitory neurons could underlie the hyperexcitability of neurons. Further study is needed to test whether the L-stellate cells might be potentially damaged with the onset of hearing loss and tinnitus. If compromised, loss of such activity could lead to hyperactivity and auditory dysfunction.
This result could suggest new targets for tinnitus therapies through inhibitory neuronal activation, and insights into new prevention strategies. The identification and characterization of inhibitory cells are critical for understanding both auditory processing and the pathophysiology of tinnitus.
A 2018 Emerging Research Grants (ERG) scientist generously funded by the Les Paul Foundation, Tenzin Ngodup, Ph.D., is a postdoctoral fellow at Oregon Hearing Research Center, Oregon Health & Science University. Coauthor Lawrence O. Trussell is a 1991 ERG alumnus.
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I’d like to share four important breakthroughs in hearing research over the past year, and how each also connects back to Hearing Health Foundation, to varying degrees. These major advances offer hope for how we might improve or restore hearing and, by extension, bring a bit more of that wonderful world into everyone’s lives.