Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator

• Published in: Hearing research 2018-08, Vol.365, p.77-89
• Main Authors: Anderson, Lucy A., Hesse, Lara L., Pilati, Nadia, Bakay, Warren M.H., Alvaro, Giuseppe, Large, Charles H., McAlpine, David, Schaette, Roland, Linden, Jennifer F.
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation - methods; Acoustic trauma; Animals; Auditory Pathways - drug effects; Auditory Pathways - metabolism; Auditory Threshold - drug effects; AUT00063; Cell Line, Tumor; Dose-Response Relationship, Drug; Evoked Potentials, Auditory, Brain Stem - drug effects; Humans; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; Inferior Colliculi - drug effects; Inferior Colliculi - metabolism; Inferior colliculus; Male; Mice, Inbred CBA; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Noise exposure; Potassium channels; Pyrimidines - pharmacokinetics; Pyrimidines - pharmacology; Shaw Potassium Channels - drug effects; Shaw Potassium Channels - genetics; Shaw Potassium Channels - metabolism; Signal Transduction - drug effects; Spontaneous activity
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2018.04.012

Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice is significantly elevated four weeks following noise exposure at recording sites with frequency tuning within or near the noise exposure band, and this selective central auditory pathology can be normalised through administration of a novel compound that modulates activity of Kv3 voltage-gated ion channels. The compound had no statistically significant effect on IC spontaneous activity without noise exposure, nor on thresholds or frequency tuning of tone-evoked responses either with or without noise exposure. Administration of the compound produced some reduction in the magnitude of evoked responses to a broadband noise, but unlike effects on spontaneous rates, these effects on evoked responses were not specific to recording sites with frequency tuning within the noise exposure band. Thus, the results suggest that modulators of Kv3 channels can selectively counteract increases in spontaneous activity in the auditory midbrain associated with noise exposure. •Spontaneous activity in mouse inferior colliculus is elevated after noise exposure.•AUT00063, a novel Kv3 channel modulator, normalises this midbrain pathology.•No effect of AUT00063 on IC spontaneous activity without noise exposure.•No effect of AUT00063 on IC tone-evoked response thresholds or frequency tuning.