Deaf Mice Maintain Inner Ear Function Until Ear Canal Opens; Findings Shed Light on Cochlear Implant Effectiveness

New research conducted by scientists at Johns Hopkins Medicine shows that mice with hereditary deafness exhibit normal neural activity in the auditory system during the first two weeks of life. This early auditory activity appears to serve as a form of training for the brain to process sound once hearing begins. The study, published in the June 27 edition of PLOS Biology, may shed new light on the mechanisms underlying the success of cochlear implants in individuals with genetic hearing loss.

Scientists believe mutations in the Gjb2 gene are responsible for more than 25% of congenital hearing loss cases. The gene encodes the connexin 26 protein, which belongs to a group of proteins called GAP junctions. These proteins bridge the gap between cells, allowing them to exchange ions, metabolites, and other molecules that play a role in cell communication and maintenance.

The researchers say their findings suggest a mechanism for the observation that people with this hereditary mutation respond well to cochlear implants (CIs). CIs use electrical signals to stimulate nerves in the inner ear and can significantly improve hearing for those with more severe hearing losses and people for whom hearing aids are ineffective. According to the National Institutes of Health, over 180,000 CIs were implanted in both adults and children between December 2019 and March 2021.

The connexin 26 protein is predominantly present in supportive cells within the cochlea, the spiral-shaped organ responsible for transmitting sound to the brain. Without connexin 26, the cochlea fails to develop its normal shape and loses its ability to detect the vibrations necessary for efficient sound detection. However, despite this structural disruption, the researchers found that the cochlea can still generate spontaneous activity, which is crucial for brain development related to sound processing.

“Supportive cells are extremely important for tissues and organs,” says neuroscientist Dwight Bergles, PhD, the Diana Sylvestre and Charles Homcy Professor at the Johns Hopkins University School of Medicine. “The new study shows how critical they are for training the auditory system and getting it ready to process sound.”

Bergles and Johns Hopkins’ MD/PhD candidate Calvin Kersbergen created a mouse model lacking connexin 26 specifically in supportive cochlea cells. By measuring auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs), they found that mice lacking connexin 26 in supporting cells were deaf, highlighting the vital role of these intercellular channels in hearing.

Given this, they also wondered whether the absence of connexin 26 and changes in cochlear structure would disrupt spontaneous activity in younger mice before their ear canal opens. Surprisingly, they found that mice without connexin 26 still exhibited bursts of electrical activity in auditory neurons at levels similar to those with intact connexin 26. Further investigation revealed that the spontaneous activity in supportive cells activated sensory hair cells in the inner ear—leading to normal neuronal activity in sound-processing areas of the brain.

Batting practice for the auditory areas of the brain

Bergles suggests that the role of supportive cells during this early developmental period is to "train" the auditory system to respond to sound at specific frequencies. Although the ear canal is not yet open, supportive cells generate their own spontaneous activity to stimulate the mechanically sensitive hair cells within the fluid-filled cochlea. This self-generated activity is comparable to the cochlea producing its own "sounds" during this stage of development, aiding the maturation of auditory neurons and circuits before the ear canal becomes accessible.

“It’s as if the cochlea is producing its own ‘sounds’ at this stage of development,” says Bergles. “This practice may help the auditory neurons and circuits in the brain mature before the ear canal opens. It’s like a baseball player in a batting cage, learning the basics of their swing and preparing to face the unpredictability of a real pitcher,” says Bergles.

The researchers also observed that the spontaneous activity in supportive cells of deaf mice ceases once the ear canal opens. Simultaneously, the auditory neurons—unable to process sound—become more sensitive to sound stimuli. This heightened sensitivity is similar to hyperacusis, a condition in humans where normal sound levels can be perceived as being painful. It can also result in tinnitus or “ringing in the ears.”

The study's findings suggest a molecular basis for the improved outcomes observed in individuals with the hereditary mutation who receive cochlear implants early in life. “Spontaneous activity in supportive cells in the cochlea may provide the molecular evidence for empirical data showing better outcomes among people who have cochlear implants placed earlier in life,” says Bergles.

The research team plans to study whether they can tap into the spontaneous activity pathway in supportive cells to treat tinnitus and other auditory conditions.

Scientists Travis Babola and Patrick Kanold also contributed to the research.