Ribbon synapse plasticity in the cochleae of Guinea pigs after noise-induced silent damage

Abstract

Noise exposure at low levels or low doses can damage hair cell afferent ribbon synapses without causing permanent threshold shifts. In contrast to reports in the mouse cochleae, initial damage to ribbon synapses in the cochleae of guinea pigs is largely repairable. In the present study, we further investigated the repair process in ribbon synapses in guinea pigs after similar noise exposure. In the control samples, a small portion of afferent synapses lacked synaptic ribbons, suggesting the co-existence of conventional no-ribbon and ribbon synapses. The loss and recovery of hair cell ribbons and post-synaptic densities (PSDs) occurred in parallel, but the recovery was not complete, resulting in a permanent loss of less than 10% synapses. During the repair process, ribbons were temporally separated from the PSDs. A plastic interaction between ribbons and postsynaptic terminals may be involved in the reestablishment of synaptic contact between ribbons and PSDs, as shown by location changes in both structures. Synapse repair was associated with a breakdown in temporal processing, as reflected by poorer responses in the compound action potential (CAP) of auditory nerves to time-stress signals. Thus, deterioration in temporal processing originated from the cochlea. This deterioration developed with the recovery in hearing threshold and ribbon synapse counts, suggesting that the repaired synapses had deficits in temporal processing.

Figure 1. Confocal images of ribbons (stained red against CtBP2) and PSD95 (green) showing the noise-induced changes in numbers, sizes, and locations.

1: 1 day, 1 week, and 1 month post-noise. The short hollow arrows point to ribbons or PSDs that were not paired.

Figure 2. Noise-induced changes in the frequency distribution of ribbon counts along the cochleae.

Left: absolute values of ribbon counts. Right: normalized percentage (control values as 100%). 1 DPN, 1 WPN, and 1 MPN: 1 day, 1 week, and 1 month post-noise.

Figure 3. Noise-induced changes in the frequency distribution of PSD counts along the cochlea.

Left: absolute values of ribbon counts. Right: normalized percentage (control values as 100%). 1 DPN, 1 WPN, and 1 MPN: 1 day, 1 week, and 1 month post-noise.

Figure 4. Changes in averaged PSD/ribbon counts as a function of time versus noise.

A significant decrease in both ribbon and PSD counts was seen after the noise. The counts had not fully recovered at 1* comparison with the PSD and ribbon controls, respectively. # comparison between ribbons and PSDs.

Figure 5. Noise-induced changes in sizes of ribbons and PSDs over four frequency spots.

Figure 6. Location changes of ribbons and PSDs after noise exposure.

A larger distance between the two structures and the IHC nuclei suggests a location towards the bottom of the IHCs. **: p<0.01 for both ribbons and PSDs, compared with the control. ##: p<0.01 for the comparison between ribbons and PSDs.

Figure 7. CAP amplitude changes as a function of inter-click interval.

The CAP to the second click (CAP2) was measured in RMS. A: absolute amplitude, B: normalized amplitude ratio, using largest CAP2 as 100%. The level of clicks was 70 dB peSPL.

Figure 8. CAP2 latency as a function of ICIs.

The response was tested at a level of 70

Figure 9. Schematic of the hypothesis of ribbon synapse plasticity after destruction by noise.

We hypothesize that the noise exposure destroyed the ribbons, which were then reproduced via protein synthesis by organelles around the nuclei. The ribbons move laterally to cell membranes. Attraction between ribbons and PSDs causes downward and upward movements, respectively, of those structures. Eventually, the paired ribbon-PSDs move downwards.