Supranormal Hearing Achieved by Boosting Ear Synapses

Summary: Researchers have enhanced auditory processing in young mice by increasing inner ear synapses using neurotrophin-3. This study supports the hypothesis that synapse density impacts hidden hearing loss in humans.

The findings could lead to new treatments for hearing disorders by preserving or regenerating synapses. The study reveals that boosting synapses not only improves hearing but also enhances auditory information processing.

Key Facts:

  1. Increasing inner ear synapses in mice led to improved auditory processing.
  2. Synapse density is linked to hidden hearing loss, affecting hearing clarity in noise.
  3. This research suggests potential new treatments for hearing disorders by targeting synapses.

Source: University of Michigan

A study from Michigan Medicine’s Kresge Hearing Research Institute was able to produce supranormal hearing in mice, while also supporting a hypothesis on the cause of hidden hearing loss in humans.

The researchers had previously used similar methods—increasing the amount of the neurotrophic factor neurotrophin-3 in the inner ear—to promote the recovery of auditory responses in mice that had experienced acoustic trauma, and to improve hearing in middle-aged mice. 

Not only did they show enhanced peaks in measured Acoustic Brain Stem response, but the mice also performed better on the Gap-Prepulse Inhibition test, suggesting an ability to process an increased amount of auditory information. Credit: Neuroscience News

This study is the first to use the same approach in otherwise healthy young mice to create improved auditory processing, beyond what’s naturally occurring.

“We knew that providing Ntf3 to the inner ear in young mice increased the number of synapses between inner hair cells and auditory neurons, but we did not know what having more synapses would do to hearing,” said Gabriel Corfas, Ph.D., director of the Kresge Institute, who led the research team. 

“We now show that animals with extra inner ear synapses have normal thresholds—what an audiologist would define as normal hearing—but they can process the auditory information in supranormal ways.”

The resulting paper, “From hidden hearing loss to supranormal auditory processing by neurotrophin 3-mediated modulation of inner hair cell synapse density,” was published in PLOS Biology.

About the paper 

As in previous studies, the researchers altered the expression of the Ntf3 to increase the number of synapses between inner hair cells and neurons. 

Inner hair cells exist inside the cochlea and convert sound waves into signals sent—via those synapses—to the brain. 

This time, however, two groups of young mice were created and studied: one in which synapses were reduced, and a second—the supranormal hearing mice—in which synapses were increased.

“Previously, we have used that same molecule to regenerate synapses lost due to noise exposure in young mice, and to improve hearing in middle-aged mice, when they already start showing signs of age-related hearing loss,” said Corfas. 

“This suggests that this molecule has the potential to improve hearing in humans in similar situations. The new results indicate the regenerating synapses or increasing their numbers will improve their auditory processing.”

Both groups of mice underwent a Gap-Prepulse Inhibition test, which measures their ability to detect very brief auditory stimuli. 

For this test, the subject is placed in a chamber with a background noise, then a loud tone that startles the mouse is presented alone or preceded by a very brief silent gap. 

That gap, when detected by the mouse, reduces the startle response. Researchers then determine how long the silent gap needs to be for the mice to detect it.

Mice with fewer synapses required a much longer silent gap. That result supports a hypothesis about the relationship between synapse density and hidden hearing loss in humans. 

Hidden hearing loss describes a difficulty in hearing that cannot be detected by standard testing. 

People with hidden hearing loss may struggle to understand speech—or discern sounds in the presence of background noise. And results of the Gap-Prepulse Inhibition test had been previously shown to be correlated with auditory processing in humans. 

A surprising find

Less expected, however, were the results of the subjects with increased synapses. 

Not only did they show enhanced peaks in measured Acoustic Brain Stem response, but the mice also performed better on the Gap-Prepulse Inhibition test, suggesting an ability to process an increased amount of auditory information.

“We were surprised to find that when we increased the number of synapses, the brain was able to process the extra auditory information. And those subjects performed better than the control mice in the behavioral test,” Corfas said. 

Hair cell loss had once been believed to be the primary cause of hearing loss in humans as we age. 

Now, however, it’s understood that the loss of inner hair cell synapses can be the first event in the hearing loss process, making therapies that preserve, regenerate and/or increase synapses exciting possible approaches for treating some hearing disorders. 

“Some neurodegenerative disorders also start with loss of synapses in the brain,” Corfas said. 

“Therefore, the lessons from the studies in the inner ear could help in finding new therapies for some of these devastating diseases.” 

About this auditory neuroscience research news

Author: Sam Page
Source: University of Michigan
Contact: Sam Page – University of Michigan
Image: The image is credited to Neuroscience News

Original Research: Open access.
From hidden hearing loss to supranormal auditory processing by neurotrophin 3-mediated modulation of inner hair cell synapse density” by Gabriel Corfas et al. PLOS Biology


Abstract

From hidden hearing loss to supranormal auditory processing by neurotrophin 3-mediated modulation of inner hair cell synapse density

Loss of synapses between spiral ganglion neurons and inner hair cells (IHC synaptopathy) leads to an auditory neuropathy called hidden hearing loss (HHL) characterized by normal auditory thresholds but reduced amplitude of sound-evoked auditory potentials. It has been proposed that synaptopathy and HHL result in poor performance in challenging hearing tasks despite a normal audiogram.

However, this has only been tested in animals after exposure to noise or ototoxic drugs, which can cause deficits beyond synaptopathy. Furthermore, the impact of supernumerary synapses on auditory processing has not been evaluated.

Here, we studied mice in which IHC synapse counts were increased or decreased by altering neurotrophin 3 (Ntf3) expression in IHC supporting cells.

As we previously showed, postnatal Ntf3 knockdown or overexpression reduces or increases, respectively, IHC synapse density and suprathreshold amplitude of sound-evoked auditory potentials without changing cochlear thresholds.

We now show that IHC synapse density does not influence the magnitude of the acoustic startle reflex or its prepulse inhibition. In contrast, gap-prepulse inhibition, a behavioral test for auditory temporal processing, is reduced or enhanced according to Ntf3 expression levels. These results indicate that IHC synaptopathy causes temporal processing deficits predicted in HHL.

Furthermore, the improvement in temporal acuity achieved by increasing Ntf3 expression and synapse density suggests a therapeutic strategy for improving hearing in noise for individuals with synaptopathy of various etiologies.