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Title: Acoustic trauma slows AMPAR-mediated EPSC decay in the auditory brainstem; reducing GluA4 subunit expression as a mechanism to rescue binaural function
Authors: Pilati, Nadia
Linley, Deborah M.
Selvaskandan, Haresh
Uchitel, Osvaldo
Hennig, Matthias H.
Kopp-Scheinpflug, Cornelia
Forsythe, Ian Duncan
First Published: 22-Apr-2016
Publisher: Wiley for Physiological Society
Citation: The Journal of Physiology, 2016, 'Accepted Article', doi: 10.1113/JP271929
Abstract: 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 ± 0.11 ms, 0.77 ± 0.08 ms, respectively) in adult mice. This correlated with LSO mRNA levels for glycinergic and glutamatergic ionotropic receptor subunits; confirming a switch from Glyα2 to Glyα1 for IPSCs and increased expression of GluA3 and GluA4 subunits for EPSCs. The NMDAR-EPSC decay τ accelerated from > 40 ms in prehearing animals, to 2.6 ± 0.4 ms 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 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.
ISSN: 0022-3751
eISSN: 1469-7793
Version: Post-print
Type: Journal Article
Rights: Copyright © the authors, 2016. The file attached to this record is distributed under the Creative Commons “Attribution Non-Commercial No Derivatives” licence, further details of which can be found via the following link:
Appears in Collections:Published Articles, Dept. of Neuroscience, Psychology and Behaviour

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tjp7283.pdfPost-review (final submitted)2.03 MBAdobe PDFView/Open
Pilati_et_al_2015_final_201115.pdfPre-review (submitted draft)1.14 MBAdobe PDFView/Open
LSO_paper_figs_Legends_201115.pdfPre-review (submitted draft)1.14 MBAdobe PDFView/Open

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