MSGID: 1:317/3 649bb76d   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Deaf mice have nearly normal inner ear function until ear canal opens   
    Findings support placement of cochlear implants early in life    
      
     Date:   
         June 27, 2023   
     Source:   
         Johns Hopkins Medicine   
     Summary:   
         For the first two weeks of life, mice with a hereditary form   
         of deafness have nearly normal neural activity in the auditory   
         system, according to a new study. Previous studies indicate that   
         this early auditory activity - - before the onset of hearing --   
         provides a kind of training to prepare the brain to process sound   
         when hearing begins.   
      
      
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   FULL STORY   
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   For the first two weeks of life, mice with a hereditary form of deafness   
   have nearly normal neural activity in the auditory system, according   
   to a new study by Johns Hopkins Medicine scientists. Their previous   
   studies indicate that this early auditory activity -- before the onset   
   of hearing -- provides a kind of training to prepare the brain to process   
   sound when hearing begins.   
      
   The findings are published June 27 in PLOS Biology.   
      
   Mutations in Gjb2 cause more than a quarter of all hereditary forms of   
   hearing loss at birth in people, according to some estimates. The connexin   
   26 protein coded by the gene is in a family of proteins known as GAP   
   junctions, because these proteins span the tiny gap between cells and   
   form a kind of tube that connects two cells to trade ions, metabolites   
   and other molecules that communicate or maintain an equilibrium.   
      
   This unexpected finding, according to investigators, suggests a molecular   
   mechanism for the observation that people with this hereditary mutation   
   respond well to cochlear implants, the electronic devices that are   
   designed to mimic sound conduction in the inner ear and can improve   
   hearing in those with severe hearing loss. According to the National   
   Institutes of Health, about 118,100 cochlear implants were implanted in   
   adults and 65,000 in children between December 2019 and March 2021.   
      
   The connexin 26 protein in the cochlea, the spiral-like structure in the   
   inner ear, is highly enriched in supportive cells, which, like their   
   name implies, provide structural and nutritional help to surrounding   
   hair cells and auditory neurons.   
      
   Previous studies have shown that, without connexin 26, the cochlea fails   
   to develop its normal shape and is incapable of amplifying sound-induced   
   vibrations necessary for efficient sound detection. Despite this   
   disruption to the cochlear structure, this research shows the cochlea   
   is still capable of producing the "spontaneous" activity needed to shape   
   brain development.   
      
   "Supportive cells are extremely important for tissues and organs,"   
   says neuroscientist Dwight Bergles, Ph.D., 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."  For the study,   
   Bergles and Calvin Kersbergen, an M.D./Ph.D. candidate in Johns Hopkins'   
   Medical Scientist Training Program, created a mouse model that lacked   
   connexin 26 specifically in supportive cells in the cochlea.   
      
   By using external electrodes to measure electrical responses in the   
   auditory nerve in response to tones or clicks, they found that mice   
   lacking connexin 26 only in supportive cells of the cochlea were, indeed,   
   deaf, demonstrating the crucial role of these intercellular channels   
   in hearing.   
      
   However, Bergles and Kersbergen wondered if this change in supportive   
   cells and shape of the cochlea would also disrupt spontaneous activity   
   in younger mice, less than 2 weeks old, before their ear canal opens.   
      
   The researchers found that mice without connexin 26 still exhibit bursts   
   of electrical activity in auditory neurons at nearly the same levels as   
   young mice with intact connexin 26. Further investigation revealed that   
   spontaneous activity in supportive cells was able to activate sensory   
   hair cells in the inner ear, leading to normal neuronal activity in   
   sound-processing areas of the brain.   
      
   "Even in the absence of connexin 26, we still find robust spontaneous   
   activity in the cochlea in these young mice," says Bergles.   
      
   Bergles says there is now evidence that the role of supportive cells   
   in this early period is to "train" the auditory system to respond   
   to sound at certain frequencies. Since the ear canal isn't open yet,   
   supportive cells generate their own activity spontaneously to stimulate   
   the mechanically sensitive hair cells in the fluid-filled cochlea.   
      
   "It's as if the cochlea is producing its own 'sounds' at this stage   
   of development," Bergles says. "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.   
      
   Finally, the researchers found that spontaneous activity in supportive   
   cells of deaf mice halts once the ear canal opens. At the same time,   
   because the mice can't process sound, their auditory neurons actually   
   increase their sensitivity to sound.   
      
   This hypersensitivity to sound is similar to the phenomenon of   
   hyperacusis, in which normal levels of sound can be painful. In humans,   
   this hearing loss- induced hypersensitivity can also lead to constant   
   ringing of the ears, called tinnitus.   
      
   Bergles says the research also suggests a molecular mechanism for why   
   people with this hereditary mutation who receive cochlear implants early   
   on tend to do better than those who receive them later.   
      
   "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 this   
   research.   
      
   Funding was provided by the National Institutes of Health (F30DC018711,   
   F32DC019842, U19NS107464, R01DC009607, R01DC008860, P30NS050274).   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Hearing_Loss # Disability # Nervous_System # Stem_Cells   
             o Mind_&_Brain   
                   # Hearing_Impairment # Tinnitus # Perception # Dementia   
       * RELATED_TERMS   
             o Hearing_impairment o Sensory_system o Auditory_system o   
             Ultrasound o Brain o Functional_neuroimaging o Premature_birth   
             o Alpha_wave   
      
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   Story Source: Materials provided by Johns_Hopkins_Medicine. Note:   
   Content may be edited for style and length.   
      
      
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   Journal Reference:   
      1. Calvin J. Kersbergen, Travis A. Babola, Patrick O. Kanold, Dwight E.   
      
         Bergles. Preservation of developmental spontaneous activity enables   
         early auditory system maturation in deaf mice. PLOS Biology, 2023;   
         21 (6): e3002160 DOI: 10.1371/journal.pbio.3002160   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230627141935.htm   
      
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