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Predicting Cochlear Synaptopathy in Mice with Varying Degrees of Outer Hair Cell Dysfunction Using Auditory Evoked
Brad N Buran1, Seán Elkins2, Wenxuan He2
1Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR, USA. buran@ohsu.edu.
Journal of the Association for Research in Otolaryngology : JARO
|December 13, 2025
Summary
Rectangular amplitude modulated envelope following response (RAM EFR) and auditory brainstem response (ABR) show promise for predicting cochlear synapse loss, even with outer hair cell dysfunction.
Area of Science:
- Auditory Neuroscience
- Otoacoustic Emissions
- Neurophysiology
Background:
- Cochlear synapse numbers decrease with age and noise, but diagnostic methods are lacking.
- Animal models link cochlear synaptopathy to reduced auditory brainstem response (ABR) wave 1 and envelope following response (EFR) to sinusoidally amplitude modulated (SAM) tones.
- SAM EFR at 1000 Hz is challenging in humans, and rectangular amplitude modulated (RAM) EFR requires validation for synaptopathy detection, especially when outer hair cell (OHC) dysfunction is present.
Purpose of the Study:
- Evaluate ABR and EFR measures for predicting cochlear synapse numbers in mice.
- Assess the robustness of diagnostic assays to outer hair cell (OHC) dysfunction.
- Compare the efficacy of SAM EFR and RAM EFR in predicting synaptopathy.
Main Methods:
- Recorded distortion product otoacoustic emissions (DPOAEs), ABR, SAM EFR, and RAM EFR in 57 mice.
- Utilized cross-validation and linear regression to model synapse number predictions.
- Histological confirmation of synapse counts.
Main Results:
- RAM EFR at 1000 Hz was the best single predictor of broad synapse loss.
- Combining RAM EFR with ABR improved synapse number predictions.
- ABR was the best predictor for focal synaptopathy.
- DPOAEs enhanced EFR predictions but not ABR predictions.
Conclusions:
- RAM EFR, ABR, and DPOAEs are valuable tools for predicting cochlear synapse numbers.
- These measures offer potential for diagnosing synaptopathy even with co-occurring OHC dysfunction.
Related Concept Videos
01:22Hair Cells
Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
01:13The Cochlea
The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.