A recent study conducted at Michigan Medicine’s Kresge Hearing Research Institute has successfully enhanced the hearing ability of mice, while also providing evidence to support a theory about hidden hearing loss in humans.
Using a technique that involved increasing the levels of a neurotrophic factor called neurotrophin-3 in the inner ear, the researchers were able to restore auditory responses in mice that had been exposed to loud noises, as well as improve their overall hearing. This method had been previously used by the same researchers to help mice recover from acoustic trauma.A recent study conducted on middle-aged mice found that providing Ntf3 to the inner ear led to improved auditory processing. This is the first study of its kind to use the same approach in otherwise healthy young mice, resulting in enhanced auditory processing beyond what occurs naturally. Gabriel Corfas, Ph.D., who led the research team at the Kresge Institute, stated that while they already knew that providing Ntf3 to the inner ear in young mice increased the number of synapses between inner hair cells and auditory neurons, they were uncertain about its impact on hearing. The study now shows that animals with extra inner ear synapses have normal hearing thresholds, despite having more synapses.The researchers published a paper in PLOS Biology titled “From hidden hearing loss to supranormal auditory processing by neurotrophin 3-mediated modulation of inner hair cell synapse density.” In this paper, they focused on altering the expression of Ntf3 to increase the number of synapses between inner hair cells and neurons. Inner hair cells are located in the cochlea and are responsible for converting sound waves into signals that are sent to the brain through these synapses.Groups of young mice were divided into two categories for study: one group had a reduction in synapses, while the other group, known as the supranormal hearing mice, had an increase in synapses. Corfas stated that the same molecule had been used to regenerate lost synapses in young mice due to noise exposure and to improve hearing in middle-aged mice with age-related hearing loss. These findings suggest that the molecule has the potential to improve human hearing in similar situations. The study also showed that regenerating synapses or increasing their numbers can enhance auditory processing.Groups of mice were tested using the Gap-Prepulse Inhibition test to measure their ability to detect short auditory stimuli. In the test, the mice were placed in a chamber with background noise, and then a loud tone was presented either alone or preceded by a brief silent gap. The researchers assessed how long the silent gap needed to be for the mice to detect it, and found that mice with fewer synapses needed a much longer silent gap. This result supports a hypothesis about the relationship between synapse density and the ability to detect auditory stimuli.The study focused on hidden hearing loss in humans, which refers to a difficulty in hearing that cannot be detected through standard testing. Individuals with hidden hearing loss may struggle to understand speech or distinguish sounds when there is background noise. Previous research has shown that the results of the Gap-Prepulse Inhibition test are linked to auditory processing in humans.
One surprising discovery in the study was the results from subjects with increased synapses. Not only did they show heightened peaks in the measured Acoustic Brain Stem response, but the mice also performed better during behavioral tests.Recent findings on the Gap-Prepulse Inhibition test have indicated an improved ability to process a higher amount of auditory information. The study revealed that increasing the number of synapses in the brain allowed for better processing of extra auditory information, leading to better performance in the behavioral test. This was a surprising discovery, as it was previously believed that hair cell loss was the main cause of age-related hearing loss in humans. Now, it is understood that the loss of inner hair cell synapses can actually be the first step in the hearing loss process, highlighting the importance of therapies that can preserve, regenerate, and increase these synapses.Researchers are exploring potential strategies for treating certain hearing disorders by targeting synapses. According to Corfas, some neurodegenerative diseases begin with a decrease in brain synapses. Therefore, the insights gained from inner ear studies may aid in the development of new treatments for these serious conditions.
