Journal Club: In vivo imaging of calcium waves in the inner hair cells and supporting cells of the cochlea!

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Today's journal article

De Faveri F, Ceriani F, Marcotti W. In vivo spontaneous Ca2+ activity in the pre-hearing mammalian cochlea. 

Why I picked this article

Another Nature Communication article on hearing!! Simply put, the methodology of this study to conduct live imaging of auditory sensory cells in the cochlea in the live animal model is amazing. 

Our peripheral auditory system, the cochlea, has specialised sensory cells called hair cells. Hair cells detect sounds by converting the mechanical vibration of sounds into electrical signals. Then the connection between hair cells and auditory neurons allows the perception of "sound" by the brain. The synaptic connections between hair cells and auditory neurons are 

During the development of the cochlea, there is a movement of Ca2+ ions, or "Ca2+ wave", in the cochlea. 

Some of the research findings

Experimental model:

  • Genetically engineered mouse, in which target cells of the cochlea have an artificial protein called "GCaMP6". 
    • Inner hair cell imaging: GCaMP6f fl/fl crossed with Myo15Cre+/− or Atoh1Cre+/−  
    • Supporting cell imaging: GCaMP6f fl/fl crossed with Pax2Cre+/−
    • Auditory nerve terminal (afferent): Snap25-GCaMP6s or GCaMP6fl/fl crossed with flNeuroD1Cre+/- mice
  • Using GCaMP6, which emits signals when there is a lot of Ca2+, the research team monitored the Ca2+ waves in the developing cochlea. 
  • Cochlea was surgically accessed without disrupting the lateral wall membrane, to preserve cochlear compartments (containing perilymph and endolymph. 
  • A part of the cochlea corresponding to 8-18kHz hearing in the mature animal was exposed for imaging. 

From Figure 1. Faveri, Ceriani & Marcotti (2025)


Inner hair cells:

  • Spontaneous Ca2+ change was observed at an average rate of 0.99 events per minute (postnatal day 3-10 old). Single event was on average 1.5 seconds long, but sometimes lasted several seconds. 
  • The spontaneous Ca2+ change dissapeared after postnatal day 12 (~ the hearing onset). 
  • Authors also compared in vivo (in live animal) and ex vivo (cultured cochlea) setups and found that Ca2+ overload seems to happen in the ex vivo setup. 
  • Using the in vivo live-animal imaging, the authors described that a synchronised Ca2+ activity across more than three inner hair cells occurred in 58% of the time. On average, seven inner hair cells were recruited together in a Ca2+ wave. 

Supporting cells:

  • Researchers also observed spontaneous Ca2+ change in supporting cells. 
  • The rate of Ca2+ change in supporting cells did not change very much with age, contrary to previous ex vivo studies, and disappeared by postnatal day 12.
  • Authors also observed a very widespread Ca2+ wave between supporting and inner hair cells, which seems to increase the number of auditory nerves forming connections. 
Overall, this study provided a detailed description of Ca2+ waves observed in inner hair cells, supporting cells in the live cochlea during development (including how many cells, frequency and duration of Ca2+ waves. 

Haruna's takeaway

There is so much nice descriptive data, and this is the type of publication I probably want to read more times, draw my own schematic and try to fully appreciate what it could mean. Data from this paper not only provides important data to provide "live system" data to compare and review ex vivo data, but also provides great input reference data for any engineers investigating the Ca2+ change in the cochlea in computer models. 

Very exciting, and I would love to one day see this experiment live! 

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This is Haruna's 9/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.