Neural Response Recovery Despite Persistent Cochlear Synaptopathy After Noise Exposure

Abstract

Synaptopathic noise exposure may preferentially target low-spontaneous rate auditory neurons. Here, we report on two models of noise-induced synaptopathy in gerbil in which hair cells remain intact and two that use higher-level exposures to produce outer hair cell (OHC) damage/loss in the cochlear base, where synaptopathy also is greatest. For all models, with and without hair cell damage, we consider a battery of functional measures that may help predict the extent and frequency location of synapse loss, as well as the nature of the fibers/synapses affected and their patterns of recovery. Experiments were conducted in Mongolian gerbil, an animal with a range of hearing sensitivity largely overlapping human, with known cochlear distributions of auditory nerve fibers by spontaneous rate (SR) subtype. Animals were noise-exposed then tested, with age-matched controls, at post-exposure time points from 24 hr to 36 wk. We recorded sound-evoked distortion product otoacoustic emissions (DPOAEs), compound action potentials (CAPs), and peri-stimulus time responses (PSTRs) across a broad range of frequencies, as well as unstimulated spontaneous neural activity. Hair cells and afferent synapses were quantified in immunolabeled cochlear tissue. A single 2-hour octave-band noise exposure at 100 or 103 dB SPL yielded threshold shifts and response amplitude reductions (DPOAE, CAP) that recovered by 2wk post exposure, without hair cell loss. High-SR-dominated CAP and PSTR peak responses and spontaneous neural noise all recovered, exceeding control values at some post-exposure times. PSTR plateaus, reflecting contributions of neurons from all subgroups, also recovered but never exceeded controls. In the same ears, synapse loss was persistent, even 36 wk post exposure. With increased exposure level, synaptopathy was accompanied by permanent threshold shifts and persistent OHC injury or frank loss. After the 112 dB SPL exposure, permanent threshold shifts and mild OHC loss were restricted to the highest frequencies/cochlear regions evaluated. CAP amplitudes recovered more fully than DPOAE amplitudes. PSTR peaks and even plateaus were like control by 36 wk. Following the 115 dB SPL exposure, large threshold shifts and suprathreshold amplitude declines remained evident at the longest post exposure time. OHC loss was largest in the extreme base. For both higher-level exposures, spontaneous neural noise declined significantly, with incomplete post-noise recovery. For a range of noise exposure levels, we observed persistent synaptopathy with recovery of neural response thresholds and amplitudes and augmented spontaneous activity. Through multiple functional assays and offline analyses, we focused on characterizing these neural responses. Post-noise recovery and even overshoot of control values for high-SR dominated onset responses was surprising given the synapse loss evident even in our longest held animals, perhaps signifying a compensatory mechanism. Our data suggest that there may be a range of noise doses that activates such a dynamic recovery process, whereas other exposures may be too low to activate it or too damaging to benefit from it.