Authors: Jérôme Bourien¹
¹Institute for Neurosciences of Montpellier
Background: Synaptic transmission between inner hair cells (IHCs) and type I auditory nerve fibers (ANFs) is primarily glutamatergic. Excessive glutamate release causes excitotoxicity, leading to neural damage. While the pathophysiology of this process is well-documented, the potential for long-term reversibility of the resulting neural damage in the mammalian cochlea remains an unresolved question in auditory neuroscience.
Method: To simulate severe excitotoxic insult, the study assessed long-term structural and functional outcomes of kainate application (25 mM) in the gerbil cochlea. This model allowed for the longitudinal observation of IHC synapses and auditory nerve function following a controlled neurotoxic event.
Results: Despite a permanent 40% reduction in IHC synapses across the tonotopic axis, the compound action potential (CAP) of the auditory nerve showed complete recovery. This functional restoration was driven by a phenotypic shift in surviving ANFs: activation thresholds were enhanced globally, and surviving low-spontaneous rate (SR) fibers in the basal region transformed to display sound-driven activity indistinguishable from high-SR fibers. In the apical region, high-SR fibers became the predominant population.
Conclusion: Compensatory phenotypic adaptation in auditory neurons enables full recovery of neural response thresholds and amplitudes despite chronic synaptopathy. However, this peripheral hyper-responsiveness likely acts as a driver for central auditory hyperactivity, providing a mechanistic link between excitotoxic injury and the subsequent development of tinnitus and hyperacusis.