"I hear you, but I don't understand you"

A recent study by researchers at the Hearing Institute at the reConnect Institute has highlighted the role of the OTOGL gene in auditory hyperexcitability, which can manifest itself in humans as tinnitus or hyperacusis, for example. They also identified a subpopulation of neurons involved in controlling the ear's protective reflexes.

@Sabrina Mechaussier

Deafness is the most common sensory impairment, currently affecting over 6% of the world’s population. According to the projections, over 700 million people will be affected by 2050.

In most cases, hearing impairment is linked to dysfunction of the auditory sensory cells, resulting in abnormal hearing thresholds.

Auditory neuropathies, on the other hand, are difficult to detect because they are accompanied by normal hearing thresholds, hence their name, hidden deafness. They are caused by damage to the auditory nerve, with or without a loss of sensory cells. They represent 10% of cases in France, that being 600 000 patients.

This disorder leads to difficulties in understanding speech or in locating the sound source. 

In the study published on May 22nd, researchers at the Hearing Institute discovered that, despite apparently normal hearing, mice with a mutation in the gene encoding otogelin-like (OTOGL) displayed auditory hyperexcitability manifesting by reflex epileptic seizures induced by loud sounds. In humans, the auditory hyperexcitability can manifest by less extreme pathologies such as tinnitus, the perception of phantom sounds, or hyperacusis, an unpleasant or even painful perception of sounds of moderate intensity that are usually well-tolerated.

By studying the origin of this hyperexcitability, the researchers identified a subpopulation of neurons involved in the processing of loud sounds, and in the control of the ear’s protective reflexes against loud sounds called the stapedial reflex.

In otogelin-like mutant mice, the activation threshold of these neurons is raised, leading to an elevation in the activation threshold of the normally protective ear reflex.

These results reveal how much damage to a population of auditory nerve neurons, i.e. auditory neuropathy, a hidden deafness, can manifest as auditory hyperexcitability.

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Gagliardini, M., Mechaussier, S., Campos Pina, C., Morais, M., Postal, O., Jean, P., Dupont, T., Singh-Estivalet, A., Udugampolage, S., Scandola, C., Verpy, E., Libé-Philippot, B., Inbar, T. C., Schwenkgrub, J., Spinola, C. M. B., Etournay, R., El-Amraoui, A., Bathellier, B., Mallet, A., … Michalski, N. (2025). Deciphering Auditory Hyperexcitability in Otogl Mutant Mice Unravels an Auditory Neuropathy Mechanism. Advanced Science, 12(19), 2410776. https://doi.org/10.1002/advs.202410776