Journal Club: Infrared light stimulates outer hair cell electromotility to trigger infrared-triggered cochlear response.

on

Today's journal article

Azimzadeh JB, Quiñones PM, Oghalai JS, Ricci AJ. Infrared light stimulates the cochlea through a mechanical displacement detected and amplified by hair cells. 

Why I picked this article

Cochlear implants are a highly successful technology, where the electrical electrodes inserted into the cochlea stimulate auditory nerves. Cochlear implants can restore the sense of hearing in many of those with profound sensorineural hearing loss. One of the current limitations of cochlear implants and next step for improvements is the limited sound resolution or selectivity, given by the cochlear implant. As a cochlear implant uses an electrical signal to stimulate the auditory nerve, how the electrical current spreads in the cochlear fluids can pose a limitation for the selectivity. That smearing of the electrical signal limits spectral resolution for the cochlear implants, and this is thought to limit the use of cochlear implants in capturing complex sounds in cochlear implant users.

In this regard, infrared stimulation has been floated as a sharper, light-based alternative to using electrical current. In the cochlea, the use of infrared light to stimulate the auditory nerve has been demonstrated in the past, although the mechanism of how exactly infrared light stimulates auditory response is not known. There’s been a key dispute about whether the infrared light directly stimulates the auditory nerve or if it stimulates sensory hair cells upstream of neurons. This research investigates the mechanism of infrared stimulation of the cochlea and identifies that it involves sensory hair cells. 

Some of the research findings

Animal models:
  • CBA/CaJ wild type mice 
  • C57Bl6 wild type mice 
  • FVB/C57Bl6 mixed background B6.Cg-Pou4f3tm1.1(HBEGF)Jsto/RubelJ (Pou4f3+/DTR)
  • C57Bl6 VGLUT3 knockout mice
  • C57Bl6 TMC1 knockout mice
  • C57Bl6 TectaC1509G/C1509G mice
Stimulation of the cochlea:
  • Otic bullae was opened to expose the middle ear of the animal, and an optical fibre was used. 
  • Optical fibre: (A 400 μm (P400-2-VIS-NIR, Ocean Optics) or 200 μm optical fiber (P200-2-
  • VIS-NIR, Ocean Optics).
  • Optical fibre was placed against the otic capsule (= bone surrounding the cochlea) aiming towards the modiolus (centre portion of the cochlea where auditory nerves are) of the low-frequency zone.
  • The auditory brainstem response was recorded.
  • The compound action potential was recorded using a silver ball electrode in the round window (the sternocleidomastoid electrode)
  • Finding: Infrared stimulation of increasing intensity (109mg/cm2 - 7mj/cm2) evokes a response from the cochlea. With an increase in laser power, there is an increase in response size. 
Mechanism of infrared-evoked response: 
  • C57Bl6 VGLUT3 knockout mice: the synaptic transmission between inner hair cells and auditory neurons is abolished. In those mice, the neural component of the infrared-triggered response was abolished. Data suggest that the neural response depends on hair-cell synaptic output.
  • B6.Cg-Pou4f3tm1.1(HBEGF)Jsto/RubelJ (Pou4f3+/DTR) mice: lacks hair cells - this also abolished the infrared-evoked cochlear response. 
  • C57Bl6 TMC1 knockout mice & separate experiment using salicylate injection: block mechanotransduction abolished all infrared-evoked cochlear response. 
  • OCT imaging: infrared light induces motion of the basilar membrane. The outer hair cells had the largest motion.
Overall, this research demonstrates that the infrared light does not directly excite auditory neurons in this preparation. Instead, the infrared light acts mechanically on the organ of Corti, engaging hair-bundle transduction. Synaptic transmission from hair cells to the auditory nerve subsequently leads to cochlear nerve stimulation. 
Parts of Figure 5. The location of the motion induced by infrared stimulation. Azimzadeh et al. 2025

Haruna's takeaway

This is another massive research!! The experiment itself is highly challenging, with the surgical use of fibre optic, measurements from electrophysiology, all of which need to work well. This is further combined with the use of multiple genetically modified animal models to tease out the potential mechanism of infrared-induced stimulation of the cochlea. Amazing and very nice research publication. 

Thoughts of light-based stimulation of the cochlea are very exciting. And I am now very curious how infrared light stimulates outer hair cells. It was mentioned in the introduction of the manuscript that the infrared light can stimulate cells in a broad range of organs. I wonder if/what cellular mechanisms are known in those tissues!

 ------- 

This is Haruna's 61/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.