Scientific reports, 2017-12, Vol.7 (1), p.17496-15, Article 17496
2017
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Details
- Autor(en) / Beteiligte
- Titel
- Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage
- Ist Teil von
- Scientific reports, 2017-12, Vol.7 (1), p.17496-15, Article 17496
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Higher stages of central auditory processing compensate for a loss of cochlear nerve synapses by increasing the gain on remaining afferent inputs, thereby restoring firing rate codes for rudimentary sound features. The benefits of this compensatory plasticity are limited, as the recovery of precise temporal coding is comparatively modest. We reasoned that persistent temporal coding deficits could be ameliorated through modulation of voltage-gated potassium (Kv) channels that regulate temporal firing patterns. Here, we characterize AUT00063, a pharmacological compound that modulates Kv3.1, a high-threshold channel expressed in fast-spiking neurons throughout the central auditory pathway. Patch clamp recordings from auditory brainstem neurons and in silico modeling revealed that application of AUT00063 reduced action potential timing variability and improved temporal coding precision. Systemic injections of AUT00063 in vivo improved auditory synchronization and supported more accurate decoding of temporal sound features in the inferior colliculus and auditory cortex in adult mice with a near-complete loss of auditory nerve afferent synapses in the contralateral ear. These findings suggest modulating Kv3.1 in central neurons could be a promising therapeutic approach to mitigate temporal processing deficits that commonly accompany aging, tinnitus, ototoxic drug exposure or noise damage.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-017-17406-xTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5727503
- Format
- –
- Schlagworte
- Action potential, Action Potentials - drug effects, Aging, Animals, Auditory nerve, Auditory Pathways - drug effects, Auditory Pathways - injuries, Auditory Pathways - metabolism, Auditory Perception - drug effects, Auditory Perception - physiology, Auditory plasticity, Brain stem, Cochlea, Cochlear Nerve - injuries, Cochlear Nerve - metabolism, Compulsive Behavior, Cortex (auditory), Disease Models, Animal, Firing pattern, Hair, Imidazoles - pharmacology, Inferior colliculus, Information processing, Membrane Transport Modulators - pharmacology, Mesencephalon, Mesencephalon - drug effects, Mesencephalon - metabolism, Mice, Models, Biological, Neural coding, Neurons, Neurons - drug effects, Neurons - metabolism, Noise, Ototoxicity, Ouabain, Potassium, Potassium channels, Potassium channels (voltage-gated), Pyrimidines - pharmacology, Recovery of Function - drug effects, Sensory neurons, Shaw Potassium Channels - metabolism, Sound, Synchronization, Temporal cortex, Temporal variations, Tinnitus, Tissue Culture Techniques, Vestibulocochlear Nerve Diseases - drug therapy, Vestibulocochlear Nerve Diseases - metabolism