Synaptic migration and reorganization after noise exposure suggests regeneration in a mature mammalian cochlea

Tyler T Hickman,Ken Hashimoto,Leslie D Liberman,M Charles Liberman

doi:10.1038/s41598-020-76553-w

Tyler T Hickman, Ken Hashimoto + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-76553-w

Copy DOI

Abstract

Overexposure to intense noise can destroy the synapses between auditory nerve fibers and their hair cell targets without destroying the hair cells themselves. In adult mice, this synaptopathy is immediate and largely irreversible, whereas, in guinea pigs, counts of immunostained synaptic puncta can recover with increasing post-exposure survival. Here, we asked whether this recovery simply reflects changes in synaptic immunostaining, or whether there is actual retraction and extension of neurites and/or synaptogenesis. Analysis of the numbers, sizes and spatial distribution of pre- and post-synaptic markers on cochlear inner hair cells, in guinea pigs surviving from 1 day to 6 months after a synaptopathic exposure, shows dramatic synaptic re-organization during the recovery period in which synapse counts recover from 16 to 91% of normal in the most affected regions. Synaptic puncta move all over the hair cell membrane during recovery, translocating far from their normal positions at the basolateral pole, and auditory-nerve terminals extend towards the hair cell’s apical end to re-establish contact with them. These observations provide stronger evidence for spontaneous neural regeneration in a mature mammalian cochlea than can be inferred from synaptic counts alone.

Highlights

Overexposure to intense noise can destroy the synapses between auditory nerve fibers and their hair cell targets without destroying the hair cells themselves
Our aim was to clarify whether this noise-induced decrease and increase in synaptic puncta counts in guinea pig reflects a recovery process or a regeneration process, i.e. whether destruction and reconstruction of auditory nerve fibers (ANFs) synapses really occurs after noise exposure in an adult mammalian ear
In the group evaluated at 1 week post exposure, thresholds had recovered to within 13 dB of baseline measures (Fig. 1b), whether measured by CAPs or DPOAEs

Summary

Introduction

Overexposure to intense noise can destroy the synapses between auditory nerve fibers and their hair cell targets without destroying the hair cells themselves In adult mice, this synaptopathy is immediate and largely irreversible, whereas, in guinea pigs, counts of immunostained synaptic puncta can recover with increasing post-exposure survival. Even exposures causing only transient threshold elevation, and no hair cell death, can destroy synaptic connections between auditory nerve fibers (ANFs) and inner hair cells (IHCs). These synaptic connections normally drive the fast signal transmission required for encoding of acoustic s ignals[6]. In our studies of noise-exposed mice, immunostaining intensity of surviving synaptic

Objectives

Methods

Results

Conclusion