A study from Michigan Medicine’s Kresge Hearing Research Institute was able to produce supranormal hearing in mice, while supporting a hypothesis about the cause of hidden hearing loss in humans.
Researchers had previously used similar methods (increasing the amount of the neurotrophic factor neurotrophin-3 in the inner ear) to promote recovery of auditory responses in mice that had experienced acoustic trauma and to improve hearing in middle-aged mice.
This study is the first to use the same approach in young, otherwise healthy mice to create enhanced auditory processing, beyond what occurs naturally.
“We knew that providing Ntf3 to the inner ear of young mice increased the number of synapses between inner hair cells and auditory neurons, but we didn’t know what effects having more synapses would have on hearing,” said Gabriel Corfas, Ph.D., director. of the Kresge Institute, who led the research team.
“We now show that animals with extra synapses in the inner ear have normal thresholds (what an audiologist would define as normal hearing), but can process auditory information in a supranormal manner.”
The resulting paper, “From hidden hearing loss to supernormal auditory processing via neurotrophin 3-mediated modulation of inner hair cell synapse density,” was published in More biology.
on paper
As in previous studies, the researchers altered Ntf3 expression to increase the number of synapses between inner hair cells and neurons.
Inner hair cells exist within the cochlea and convert sound waves into signals sent, through 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 mice with supernormal hearing) 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 are already beginning to show signs of age-related hearing loss,” Corfas said. .
“This suggests that this molecule has the potential to improve hearing in humans in similar situations. The new results indicate that regenerating synapses or increasing their number 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 background noise, then a loud tone is presented that startles the mouse either alone or preceded by a brief silence.
That gap, when detected by the mouse, reduces the startle response. The researchers then determine how long the silent gap must last for the mice to detect it.
Mice with fewer synapses required a much longer silent interval. This 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 tests.
People with hidden hearing loss may have difficulty understanding speech or discerning sounds in the presence of background noise. And gap prepulse inhibition test results had previously been shown to correlate with auditory processing in humans.
A surprising find
However, less expected were the results for subjects with increased synapses.
Not only did they show enhanced peaks in the measured acoustic brainstem response, but the mice also performed better on the gap prepulse inhibition test, suggesting an ability to process a greater amount of auditory information.
“We were surprised to find that when we increased the number of synapses, the brain was able to process additional auditory information. And those subjects performed better than control mice on the behavioral test,” Corfas said.
Hair cell loss was once thought to be the primary cause of hearing loss in humans as we age.
It is now understood, however, that loss of inner hair cell synapses may be the first event in the process of hearing loss, making therapies that preserve, regenerate, and/or augment synapses interesting potential approaches. to treat some hearing disorders.
“Some neurodegenerative disorders also begin with the loss of synapses in the brain,” Corfas said.
“Therefore, lessons from inner ear studies could help find new therapies for some of these devastating diseases.”