Researchers have produced supranormal hearing in mice, and the work also supports a hypothesis on the cause of hidden hearing loss in humans.
The researchers increased the amount of neurotrophic factor neurotrophin-3 (Ntf3) in the inner ear to create improved auditory processing beyond what is naturally occurring.
They used similar methods ten years ago to promote the recovery of auditory responses in mice that had experienced acoustic trauma, and two years ago to improve hearing in middle-aged mice and slow age-related hearing.
This study, published in PLOS Biology on 27 June 2024, was the first to use the same approach in otherwise healthy young mice.
The research team was from Michigan Medicine’s Kresge Hearing Research Institute in the US.
“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 Dr Gabriel Corfas PhD, director of the institute.
“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.”
Dr Corfas is also the institute’s Associate Chair of Research, Department of Otolaryngology-Head and Neck Surgery, Professor, Department of Otolaryngology-Head and Neck Surgery and The Lynn and Ruth Townsend Professor of Communication Disorders.
As in the previous studies, the researchers altered expression of 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 the synapses to the brain.
This time two groups of young mice were created and studied. One group had reduced synapses while the other – the supranormal hearing mice—had increased synapses.
“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,” Dr 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 numbers will improve their auditory processing.”
Hidden hearing loss
Both groups of mice underwent a Gap-Prepulse Inhibition test to measure ability to detect very brief auditory stimuli by placing the mouse 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.
The gap, when detected by the mouse, reduces the startle response. Researchers then determine how long the silent gap needs to be for the mouse to detect it.
Mice with fewer synapses required a much longer silent gap. Researchers said that result supported a hypothesis about the relationship between synapse density and hidden hearing loss in humans which 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. Results of the Gap-Prepulse Inhibition test have previously shown to be correlated with auditory processing in humans.
Less expected were results of mice with increased synapses which showed enhanced peaks in measured Acoustic Brain Stem response and better performance 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 behavioural test,” Dr Corfas said.
He said 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 started with loss of synapses in the brain so studies in the inner ear may also help find new therapies for some of those diseases, he added.
