Contrasting mechanisms for hidden hearing loss: Synaptopathy vs myelin defects.
Maral BudakKarl GroshAritra SasmalGabriel CorfasMichal ZochowskiVictoria BoothPublished in: PLoS computational biology (2021)
Hidden hearing loss (HHL) is an auditory neuropathy characterized by normal hearing thresholds but reduced amplitudes of the sound-evoked auditory nerve compound action potential (CAP). In animal models, HHL can be caused by moderate noise exposure or aging, which induces loss of inner hair cell (IHC) synapses. In contrast, recent evidence has shown that transient loss of cochlear Schwann cells also causes permanent auditory deficits in mice with similarities to HHL. Histological analysis of the cochlea after auditory nerve remyelination showed a permanent disruption of the myelination patterns at the heminode of type I spiral ganglion neuron (SGN) peripheral terminals, suggesting that this defect could be contributing to HHL. To shed light on the mechanisms of different HHL scenarios observed in animals and to test their impact on type I SGN activity, we constructed a reduced biophysical model for a population of SGN peripheral axons whose activity is driven by a well-accepted model of cochlear sound processing. We found that the amplitudes of simulated sound-evoked SGN CAPs are lower and have greater latencies when heminodes are disorganized, i.e. they occur at different distances from the hair cell rather than at the same distance as in the normal cochlea. These results confirm that disruption of heminode positions causes desynchronization of SGN spikes leading to a loss of temporal resolution and reduction of the sound-evoked SGN CAP. Another mechanism resulting in HHL is loss of IHC synapses, i.e., synaptopathy. For comparison, we simulated synaptopathy by removing high threshold IHC-SGN synapses and found that the amplitude of simulated sound-evoked SGN CAPs decreases while latencies remain unchanged, as has been observed in noise exposed animals. Thus, model results illuminate diverse disruptions caused by synaptopathy and demyelination on neural activity in auditory processing that contribute to HHL as observed in animal models and that can contribute to perceptual deficits induced by nerve damage in humans.
Keyphrases
- hearing loss
- working memory
- single cell
- peripheral nerve
- induced apoptosis
- air pollution
- magnetic resonance
- climate change
- skeletal muscle
- magnetic resonance imaging
- neuropathic pain
- high intensity
- wastewater treatment
- metabolic syndrome
- type diabetes
- adipose tissue
- computed tomography
- signaling pathway
- cell death
- single molecule
- blood brain barrier
- mesenchymal stem cells
- endoplasmic reticulum stress
- spinal cord injury
- brain injury
- cell cycle arrest
- contrast enhanced
- wild type
- chemotherapy induced
- subarachnoid hemorrhage