title: Loss of glycine receptors containing the α3 subunit compromises auditory nerve activity, but not outer hair cell function.
abstract: Inhibitory glycine receptors containing the α3 subunit (GlyRα3) regulate sensory information processing in the CNS and retina. In previous work, we demonstrated the presence of postsynaptic GlyRα3 immunoreactivity at efferent synapses of the medial and lateral olivocochlear bundle in the organ of Corti; however, the role of these α3-GlyRs in auditory signalling has remained elusive. The present study analyzes distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) of knockout mice with a targeted inactivation of the Glra3 gene (Glra3(-/-)) and their wildtype littermates (Glra3(+/+)) before and seven days after acoustic trauma (AT; 4-16 kHz, 120 dB SPL, 1 h). Before AT, DPOAE thresholds were slightly, but significantly lower, and DPOAE amplitudes were slightly larger in Glra3(-/-) as compared to Glra3(+/+) mice. While click- and f-ABR thresholds were similar in both genotypes before AT, threshold-normalized click-ABR wave I amplitudes were smaller in Glra3(-/-) mice as compared to their wildtype littermates. Following AT, both the decrement of ABR wave I amplitudes and the delay of wave I latencies were more pronounced in Glra3(-/-) than Glra3(+/+) mice. Accordingly, correlation between early click-evoked ABR signals (0-2.5 ms from stimulus onset) before and after AT was significantly reduced for Glra3(-/-) as compared to Glra3(+/+) mice. In summary, these results show that loss of α3-GlyRs compromises suprathreshold auditory nerve activity, but not outer hair cell function.
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: julia.dlugaiczyk@uks.eu.
authors.forename: Julia
authors.initials: J
authors.lastname: Dlugaiczyk
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Hecker
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Neubert
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen University Hospital, Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Buerbank
authors.affiliation: Tübingen Hearing Research Center, University of Tübingen, Tübingen, Germany.
authors.forename: Dario
authors.initials: D
authors.lastname: Campanelli
authors.affiliation: Institute for Biochemistry, Emil-Fischer Center, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Cord-Michael
authors.initials: CM
authors.lastname: Becker
authors.affiliation: Max-Planck Institute for Medical Research, Heidelberg, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Betz
authors.affiliation: Tübingen Hearing Research Center, University of Tübingen, Tübingen, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.affiliation: Tübingen Hearing Research Center, University of Tübingen, Tübingen, Germany. Electronic address: lukas.ruettiger@uni-tuebingen.de.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schick
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D003051:Cochlea / Q000502:physiology; D003056:Cochlear Nerve / Q000503:physiopathology*; D016057:Evoked Potentials, Auditory, Brain Stem; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism; D018069:Hair Cells, Vestibular / Q000473:pathology*; D006309:Hearing; D006317:Hearing Loss, Noise-Induced / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D017084:Otoacoustic Emissions, Spontaneous; D018009:Receptors, Glycine / Q000235:genetics* / Q000502:physiology; D013569:Synapses / Q000473:pathology
chemical_list: D018009:Receptors, Glycine; C113965:glycine receptor alpha3 subunit
keywords: Auditory brainstem response; Efferent olivocochlear innervation; Glycine receptor alpha3 subunit; Otoacoustic emission; Waveform correlation