Acoustic trauma slows AMPAR-mediated EPSCs in the auditory brainstem, reducing GluA4 subunit expression as a mechanism to rescue binaural function

Damaging levels of sound (acoustic trauma, AT) diminish peripheral synapses, but what is the impact on the central auditory pathway? Developmental maturation of synaptic function and hearing were characterized in the mouse lateral superior olive (LSO) from P7 to P96 using voltage-clamp and auditory brainstem responses (ABR). IPSCs and EPSCs show rapid acceleration during development, so that decay kinetics converge to similar sub-millisecond time-constants (τ, 0.87±0.11ms, 0.77±0.08ms, respectively) in adult mice. This correlated with LSO mRNA levels for glycinergic and glutamatergic ionotropic receptor subunits; confirming a switch from Gly2 to Gly1 for IPSCs and increased expression of GluA3 and GluA4 subunits for EPSCs. The NMDAR-EPSC decay τ accelerated from >40ms in prehearing animals, to 2.6±0.4ms in adults, as GluN2C expression increased. In vivo induction of AT at around P20, disrupted IPSC and EPSC integration in the LSO, so that one week later the AMPAR-EPSC decay was slowed and mRNA for GluA1 increased while GluA4 decreased. In contrast, GlyR IPSC and NMDAR-EPSC decay times were unchanged. Computational modelling confirmed that matched IPSC and EPSC This article is protected by copyright. All rights reserved. 4 kinetics are required to generate mature interaural level difference (IID) functions, and that longer-lasting EPSCs compensates to maintain binaural function with raised auditory thresholds after AT. We conclude that LSO excitatory and inhibitory synaptic drive matures to identical time-courses; that AT changes synaptic AMPARs by expression of subunits with slow kinetics (which recover over two months) and that loud sounds reversibly modify excitatory synapses in the brain, changing synaptic function for several weeks after exposure.