Auditory System

A Balancing Act Before the Onset of Hearing

By Sonja J. Pyott, Ph.D.

Our ability to hear relies on the proper connections between the sensory hair cells in the inner ear and the brain. Activity of the sensory hair cells (red) and these connections ( green) before hearing begins is essential for the proper development of hearing. The research conducted by Sonja J. Pyott, Ph.D., and colleagues investigated the mechanisms that regulate this activity.

Our ability to hear relies on the proper connections between the sensory hair cells in the inner ear and the brain. Activity of the sensory hair cells (red) and these connections ( green) before hearing begins is essential for the proper development of hearing. The research conducted by Sonja J. Pyott, Ph.D., and colleagues investigated the mechanisms that regulate this activity.

The development of the auditory system begins in the womb and culminates in a newborn’s ability to hear upon entering the world. While the age at which hearing begins varies across mammals, the sensory structures of the inner ears are active before the onset of hearing. This activity instructs the maturation of the neural connections between the inner ear and brain, an essential component of the proper development of hearing. However, we still know very little about the mechanisms regulating the activity of these sensory structures and their neural connections, specifically during the critical period just before the onset of hearing.

In our paper, “mGluR1 enhances efferent inhibition of inner hair cells in the developing rat cochlea,” soon to be published in an upcoming issue of The Journal of Physiology, we investigate the role of glutamate, a neurotransmitter, in regulating activity of the sensory structures and their connections in the inner ear before the start of hearing.

Neurotransmitters assist in the communication between neurons and are typically classified as either excitatory or inhibitory based on their action. Excitatory action results in stimulation; inhibitory action assists in the calming of the brain. Our research found that although glutamate typically excites activity, it also elicits inhibitory activity. This dual role for glutamate occurs because it activates two distinct classes of glutamate receptors: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs).

Importantly, this dual activation balances excitatory and inhibitory activity of the sensory structures, a balance of which is likely important in the final refinement of the neural connections between the inner ear and brain prior to the onset of hearing.

As part of future research, we will further investigate the role of mGluRs, one the distinct classes of glutamate receptors, in the development of hearing. We will also investigate if mGluRs balance excitatory and inhibitory activity in the adult inner ear, similar to its role prior to the onset of hearing. Insights into these mechanisms may identify new ways to modulate activity and prevent congenital or acquired hearing loss.

Study coauthor Sonja J. Pyott, Ph.D., was a 2007 and 2008 Hearing Health Foundation Emerging Research Grants recipient.

We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.

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New Insights Into Age-Related Hearing Loss

By Ruili Xie, Ph.D.

Age-related hearing loss (ARHL), also known as presbycusis, is one of the most prevalent health conditions affecting older adults. The leading cause of ARHL is generally attributed to damage in the ear during aging, which include the loss of the inner ear’s sensory hair cells and spiral ganglion cells (SGCs).  

Hair cells act like antennae for the auditory system to receive sound information from the environment. SGCs are the nerve cells that connect the ear and the brain, with their peripheral branches receiving sound information from hair cells, and their central branches forming the auditory nerve to pass information to the brain. Recent studies showed that the terminals (endpoints) of SGC peripheral branches are vulnerable and can be damaged during aging, which are thought to be the primary cause of ARHL.    

However, the majority (over 70 percent) of SGC peripheral terminals survive normal aging. It is unclear whether, with age, sound information is reliably transmitted through the surviving SGCs to the brain; and if not, how this may contribute to ARHL.

One particular point of interest lies in the terminals of the SGC central branches (the auditory nerve synapses) that activate their target neurons in the brain. Deterioration in the information flow at these synapses with age would reduce sensory input to the brain and lead to ARHL.

For the first time, Dr. Paul B. Manis and I have found that the transmission of information from SGCs to their target neurons in the cochlear nucleus (the first auditory station in the brain) is compromised in aged mice with ARHL. The transmission process deteriorates due to abnormal calcium signaling at the central terminals of the SGCs. The study not only proposes a novel brain mechanism that underlies ARHL, but also provides new strategies in developing future clinical treatments.


Ruili Xie, Ph.D., a 2009 and 2010 Emerging Research Grants recipient, is an assistant professor in the Department of Neuroscience at the University of Toledo, in Ohio.The study “Synaptic Transmission at the Endbulb of Held Deteriorates During Age-Related Hearing Loss” appeared in The Journal of Physiology on Sept. 13, 2016.

We need your help supporting innovative hearing and balance science through our Emerging Research Grants program. Please make a contribution today.

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Hearing Beyond the Hair Cell

By Yehoash Raphael, Ph.D.

Recently, it became clear that loud signals can also damage the connecting interface between the hair cell and the auditory nerve. This interface is the synapse. When the synapse is disrupted, hearing is impaired even without the loss of hair cells, leading to a condition called synaptopathy.

Experiments using transgenic mice showed that elevating levels of a specific molecule called NT3 in the area of the synapse can heal synaptopathy caused by exposure to loud noise. Since transgenic technology is a research tool not applicable for clinical use on humans, it is now necessary to design methods for elevating NT3 in human ears, leading to repair of synaptopathy. This is an important task, because if left untreated, synaptopathy progresses to include nerve cell death and permanent hearing deficits.

One potential way to increase NT3 concentration in the cochlea is by the use of gene transfer technology, which is based on infecting cochlear cells with viruses that are engineered to secrete NT3 and not cause infections. A potential risk of this method is that the site of NT3 is not restricted to the area of the synapses affected by the synaptopathy; NT3 can influence other types of cells.

In my lab at the University of Michigan, we tested the outcome of injecting such viruses on the structure and function of normal (intact) ears. We determined that the procedure resulted in the deterioration of hearing thresholds, and the auditory nerve and its connectivity to the hair cells were also negatively affected.

This negative outcome indicates that treatment of synaptopathy should be based on a more specific way to provide NT3 in an area restricted to the synaptic region. My work with the Hearing Restoration Project is dedicated to optimization of gene transfer technology in the cochlea, and may assist in finding more detailed methods for NT3 gene transfer that better target affected cells.

More information on Dr. Raphael’s research can be found in his report, “Viral-mediated Ntf3 overexpression disrupts innervation and hearing in nondeafened guinea pig cochleae,” published in the journal Molecular Therapy—Methods & Clinical Development on August 3, 2016.

Yehoash Raphael, Ph.D., is the The R. Jamison and Betty Williams Professor at the Kresge Hearing Research Institute, in the Department of Otolaryngology–Head and Neck Surgery at the University of Michigan.

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Brain and Alzheimer's Disease Awareness Month

By Morgan Leppla

Bodies are complex systems, composed of many minute details. The human anatomy serves to remind us of the intricacies of our world. This June for Brain and Alzheimer’s Awareness Month, Hearing Health Foundation (HHF) invites you to join us in celebrating one of the most mysterious and fascinating part of the body: the brain.

For one to grasp the physiological complexity of being  human, one ought to understand how their body’s many systems work in tandem. For example, each person’s brain depends on stimulation to keep it in tip-top shape and and their bodies depend on their brains to function as they are intended to.

This is clearly a stripped down explanation of the role brains play. Of course an organism’s structure can be broken down into smaller and smaller parts, so let’s focus on one of special importance to us here at HHF, hearing.

Frank Lin, M.D., Ph.D., from Johns Hopkins University reports in 2014 that hearing loss affects brain structure, and specifically accelerates brain tissue loss. The study was conducted over a 10-year period with a sampling of people which included those with substantial hearing loss and those with normal hearing.  After analyzing years of magnetic resonance imaging scans, his conclusions suggest people with substantial hearing loss show higher rates of brain atrophy. Lin explains brain shrinkage could be the result of an “‘impoverished’ auditory cortex” since there is reduced brain stimulation in that area.

"If you want to address hearing loss well," Lin says, "you want to do it sooner rather than later. If hearing loss is potentially contributing to these differences we're seeing on an MRI, you want to treat it before these brain structural changes take place."

The human brain contains some of the most challenging biological mysteries in science (and always has). Unlocking those takes perseverance, so HHF thanks brain and hearing researchers for the time and energy devoted to rigorous research and ultimately revealing information critical to improving brain health.

Parts really do affect the health of the whole. So for the brain and beyond, please make an appointment with your hearing healthcare professional for your annual checkup and, if you are diagnosed with a hearing loss, managing it. More than just your hearing will benefit! Untreated hearing loss has been linked to dementia, depression, diabetes, falls, and heart disease.

Want to learn more about brain health? Check out last year’s blog here: Your Brain Is a Muscle: Use It or Lose It

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World Heart Day

By the Better Hearing Institute

World Heart Day is today, September 29th. In response to a growing body of research showing a link between cardiovascular and hearing health, Hearing Health Foundation and Better Hearing Institute (BHI) are urging you to check your hearing.

Raymond Hull, PhD, professor of communication sciences and disorders in audiology and neurosciences at Wichita State University, recently completed research analyzing 84 years of work from scientists worldwide on the connection between cardiovascular health and the ability to hear and understand what others are saying. Hull’s work, which reviewed 70 scientific studies, confirmed a direct link.
According to Hull, “Our entire auditory system, especially the blood vessels of the inner ear, needs an oxygen-rich nutrient supply. If it doesn't get it due to cardiovascular health problems, then hearing can be affected."  
While there are many possible causes of hearing loss, cardiovascular disease appears to exaggerate the impact of those causes and intensify the degree of hearing decline, says Hull. This compounded effect not only increases the difficulty a person experiences in perceiving what has been said, but also diminishes their ability to make sense of what they hear with speed and accuracy.

Could hearing loss be an early sign of cardiovascular disease?

Research is ongoing, but a number of findings suggest that keeping track of your hearing may help you monitor your cardiovascular health as well.

“The inner ear is so sensitive to blood flow that it is possible that abnormalities in the cardiovascular system could be noted here earlier than in other less sensitive parts of the body,” according to David R. Friedland, MD, PhD, Professor and Vice-Chair of Otolaryngology and Communication Sciences at the Medical College of Wisconsin in Milwaukee.

In Dr. Friedland’s own 2009 study, published in The Laryngoscope, he and fellow researchers found that audiogram pattern correlates strongly with cerebrovascular and peripheral arterial disease and may represent a screening test for those at risk. They even concluded that patients with low-frequency hearing loss should be regarded as at risk for cardiovascular events, and appropriate referrals should be considered.

More recently, a 2014-published study by researchers at the University of Wisconsin in Madison found that the risk of hearing impairment was significantly greater in people with underlying atherosclerosis, or hardening of the arteries, than in those without vessel abnormalities, suggesting that hearing loss may be an early sign of cardiovascular disease in apparently healthy people, according to an article in The Wall Street Journal. The study involved a large cohort of middle-aged participants and showed that hearing loss is common in people in their forties. 

3 Heart-Healthy Reasons to Get a Hearing Test

  1. Six decades of research points to heart-hearing health link: Specifically, the study authors concluded that the negative influence of impaired cardiovascular health on both the peripheral and central auditory system—and the potential positive influence of improved cardiovascular health on these same systems—have been found through a sizable body of research.

  2. The ear may be a window to the heart: Some experts find the evidence showing a link between cardiovascular and hearing health so compelling that they say the ear may be a window to the heart. They encourage collaboration between hearing care providers, cardiologists, and other healthcare professionals. Some even call on hearing care professionals to include cardiovascular health in patient case history and to measure their patients’ blood pressure.

  3. The same lifestyle behaviors that affect the heart impact hearing. A higher level of physical activity is associated with a lower risk of hearing loss in women. Another revealed that smokers and passive smokers are more likely to suffer hearing loss. And a third found that regular fish consumption and higher intake of long-chain omega-3 polyunsaturated fatty acids are associated with a lower risk of hearing loss in women. Coincidence? Or does it all come back to blood flow to the inner ear? Research is ongoing.

The content for this blog post originated in a press release issued by The Better Hearing Institute on September 15, 2015.

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What Animals Can Tell Us About Humans

By Yishane Lee

Recent findings in mice by University at Buffalo scientists may one day help us better understand human hearing loss. Mice have an inner ear structure and auditory system organization similar to humans, and they also progressively lose their hearing as they age. As published in the Journal of the Acoustical Society of America in October 2014, the researchers found that mice process and understand their “ultrasonic vocalizations” (USVs), which the human ear cannot perceive, in the same way humans make sense of our own vocalizations.

Like humans (and birds), it appears that mice can distinguish a vocalization when just the beginning part is heard, versus when the end part is heard. This helps strengthen the usefulness of mice as good models for understanding human communication and hearing loss.

Dogs also have a language comprehension ability similar to humans. According to recent British study, dogs process speech in a similar way to humans: They listen to our words, not just our intonation.

According to the report, published in the journal Current Biology in November, dogs use different parts of the brain—both the left and right hemispheres—to process the verbal components of a familiar sentence and the emotion or intonation of the speaker. The study suggests that dogs pay attention to the verbal content of human speech and perceive it in a way that broadly parallels human perception. The reseachers concluded, “Dogs may share ancestral or convergent hemispheric specializations for processing the different functional communicative components of speech with human listeners.”

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