Noise exposure triggers changes in synaptic function in mammalian hair cells.

BOERO, L; PAYNE, S; GÓMEZ CASATI, ME; RUTHERFORD, M; GOUTMAN, JD

Congreso; 44RD ANNUAL MidWinter Meeting; 2021

Noise-induced hearing loss has gained relevance as one of the most important sources of hearing loss. The underlying causes of this condition have been investigated over years at histological and morphological levels, with much less progress in the physiological aspects. It has been demonstrated that noise exposure (NE) produces long-term structural damage to the inner ear, such as a reduction in the number synapses between inner hair cells (IHCs) and afferent neurons, but less is known about its impact in the ability of IHCs to signal auditory information. Here we intend to address if the capacity of IHCs to release neurotransmitter is altered after NE.Mice of either sex at ages P15-P16 (C57BL/6J VGluT3 KO or WT) were exposed to 1-12 kHz noise at 120 dB SPL, for 1 hour in a reverberant acoustic chamber. One day and 14 days after exposure mice displayed significantly increased auditory brainstem responses (ABR) thresholds as well as a strong reduction in wave 1 amplitudes. Moreover, elevation of the distortion product otoacoustic emissions (DPOAE) thresholds together with loss of outer hair cells (OHCs) in the basal region was observed in exposed mice, suggesting a noise-induced impairment of cochlear amplification. One day after exposure cochleae revealed signs of deafferentation when it was assessed by whole-mount immunostaining for CtBP2 ?the major component of the synaptic ribbon-, GluA3 ?a postsynaptic AMPA receptor subunit- and CaV1.3, to see the synaptic coupling to calcium entry.Then, we addressed the impact of NE on neurotransmitter release from IHCs by measuring Ca2+ currents and changes in membrane capacitance (ΔCm) in unexposed and one day after exposure IHCs through whole-cell patch clamp recordings. When short depolarizing pulses were applied, larger ΔCm jumps but no differences in Ca2+ currents were observed in exposed IHCs compared to controls (20.2±3.2 fF and 12.4±1.8 fF, respectively at -30 mV pulse). Increased Ca2+ cooperativity for vesicle release was observed in noise exposed mice. In addition, exposed IHC showed augmented ΔCm specially with pulses above 100 ms (for 1s pulse: 104.5±7.1 fF for control, 167.7±22.6 fF for exposed), but no differences in calcium entry were observed for any duration of depolarization. It is known that NE leads to a massive Ca2+ influx together with the release of large amounts of glutamate (that could act retrogradely). To determine which of these two was responsible for the potentiated release, we made use of the vesicular glutamate transporter Vglut3 knock-out (KO) mouse. In contrast to what was observed in WT mice, exposed KO showed reduced ΔCm compared to controls.These results suggest that noise exposure potentiated vesicle release in IHC, possibly by accelerating vesicle recruitment, and this phenomenon would be dependent upon the intense glutamate release produced during NE.