gms | German Medical Science

Background: Noise-induced cochlear synaptopathy is characterized by irreversible loss of synapses between inner hair cells (IHC) and spiral ganglion neurons despite normal hearing thresholds. We analyzed hearing performance and cochlear structure in C57BL/6N wildtype (WT) mice that had been exposed to a noise trauma ranging from 100 to 112 dB SPL for 2 h. To unravel mechanisms of synapse death, we studied ‘HA’ mice with a modified Ca_v1.3 channel Ca_v1.3DCRD^HA/HA, which carries a 30% larger peak Ca²⁺ current into hair cells. We hypothesized that increased Ca²⁺ influx per se would cause damage at IHC synapses in HA mice, and that a noise trauma would aggravate this process.

Methods: Eight-week-old mice were exposed to broadband noise (8–16 kHz) for 2 h. Auditory brainstem responses (ABR) were assessed before, directly after and 28 days post trauma. Finally, the number, size, and pairing of IHC presynaptic (CtBP2-positive) ribbons and postsynaptic AMPA receptor scaffold (Homer1-positive) clusters were analyzed along the cochlea. Non-exposed control groups of WT and HA mice served as controls.

Results: Four weeks after a 100 dB SPL trauma, a permanent threshold shift (PTS) was observed at 45 kHz in the WT group, which after the higher traumata extended towards middle to low frequencies. Frequency-specific loss of ABR wave I amplitudes scaled with trauma strength indicating loss of functional IHC synaptic connections. No trauma-related OHC loss was found. Synaptic pairs were reduced in the midbasal and basal cochlear region in all trauma conditions with ribbon loss up to 46% compared to the control group. Ribbons surviving the trauma were enlarged and paired with a postsynapse. In contrast, 4 to 6 unpaired postsynapses/IHC were found in the medial, midbasal and basal region irrespective of trauma strength.

Without any trauma, IHCs of HA mice showed normal numbers of ribbons with a 30% reduction in size in the apical, medial and midbasal region whereas ~8 ribbons/IHC were lost in the basal region. After a 106 SB SPL trauma, the numbers of ribbons and postsynapses were reduced similarly as in WT mice in the medial and midbasal region. Noise trauma led to orphan postsynapses per IHC in the range of 1–2 (medial), 4–6 (midbasal), and 3–5 (basal) in either genotype indicating that postsynapses were more stable than ribbons.

Conclusions: These data confirm the susceptibility of ribbon synapses and ABR wave I amplitudes to a noise trauma of 100 dB SPL and above. In C57BL/6N and HA mice, IHC postsynapses were more resistant than ribbons to the noise traumata applied. In the basal region of HA mice, degeneration of ribbons was observed even without acoustic trauma, yet postsynapses were hardly affected. The noise trauma did not further reduce ribbons in basal IHCs of HA mice suggesting that susceptible ribbons had already degenerated by Ca²⁺ excitotoxicity without any trauma.

Supported by DFG SFB 894 (A8).