title: Kcna1 gene deletion lowers the behavioral sensitivity of mice to small changes in sound location and increases asynchronous brainstem auditory evoked potentials but does not affect hearing thresholds.
abstract: Sound localization along the azimuth depends on the sensitivity of binaural nuclei in the auditory brainstem to small differences in interaural level and timing occurring within a submillisecond epoch and on monaural pathways that transmit level and timing cues with high temporal fidelity to insure their coincident arrival at the binaural targets. The soma and axons of these brainstem neurons are heavily invested with ion channels containing the low-threshold potassium channel subunit Kv1.1, which previous in vitro and in vivo studies suggest are important for regulating their high input-output correspondence and temporal synchrony. We compared awake Kcna1-null mutant (Kcna1-/-) mice lacking Kv1.1 with Kcna1+/+ mice to determine whether Kv1.1 activity contributes to sound localization and examined anesthetized mice for absolute hearing thresholds for suprathreshold differences that may be revealed in the waveforms of auditory brainstem response potentials. The awake -/- mice tested with reflex modification audiometry had reduced sensitivity to an abrupt change in the location of a broad band noise compared to +/+ mice, while anesthetized -/- mice had normal absolute thresholds for tone pips but a high level of stimulus-evoked but asynchronous background activity. Evoked potential waveforms had progressively earlier peaks and troughs in -/- mice, but the amplitude excursions between adjacent features were identical in the two groups. Their greater excitability and asynchrony in suprathreshold evoked potentials coupled with their normal thresholds suggests that a disruption in central neural processing in -/- mice and not peripheral hearing loss is responsible for their poor sound localization.
authors.affiliation: Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, New York 14642, USA. paul_allen@urmc.rochester.edu
authors.forename: Paul D
authors.initials: PD
authors.lastname: Allen
authors.forename: James R
authors.initials: JR
authors.lastname: Ison
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D006309:Hearing / Q000502:physiology*; D051662:Kv1.1 Potassium Channel / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D013017:Sound Localization / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C496947:Kcna1 protein, mouse; D051662:Kv1.1 Potassium Channel