Increased Spontaneous Firing Rates in Auditory Midbrain Following Noise Exposure Are Specifically Abolished by a Kv3 Channel Modulator

Publication date: Available online 30 April 2018
Source:Hearing Research
Author(s): Lucy A. Anderson, Lara L. Hesse, Nadia Pilati, Warren M.H. Bakay, Giuseppe Alvaro, Charles H. Large, David McAlpine, Roland Schaette, Jennifer F. Linden
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.



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