Auditory deficits of Kcna1 deletion are similar to those of a monaural hearing impairment

Abstract

Kv1.1 subunits of low voltage-activated (Kv) potassium channels are encoded by the Kcna1 gene and crucially determine the synaptic integration window to control the number and temporal precision of action potentials in the auditory brainstem of mammals and birds. Prior electrophysiological studies showed that auditory signaling is compromised in monaural as well as in binaural neurons of the auditory brainstem in Kv1.1 knockout mice (Kcna1(-/-)). Here we examine the behavioral effects of Kcna1 deletion on sensory tasks dependent on either binaural processing (detecting the movement of a sound source across the azimuth), monaural processing (detecting a gap in noise), as well as binaural summation of the acoustic startle reflex (ASR). Hearing thresholds measured by auditory brainstem responses (ABR) do not differ between genotypes, but our data show a much stronger performance of wild type mice (+/+) in each test during binaural hearing which was lost by temporarily inducing a unilateral hearing loss (through short term blocking of one ear) thus remarkably, leaving no significant difference between binaural and monaural hearing in Kcna1(-/-) mice. These data suggest that the behavioral effect of Kv1.1 deletion is primarily to impede binaural integration and thus to mimic monaural hearing.

Figure 1. ABR thresholds are equally elevated in Kcna1^+/+ and Kcna1^−/− mice after plugging one ear

A, B) Averaged ABR waveforms in response to 12kHz/80dB SPL tone stimulation in A) Kcna1^+/+ mice and B) Kcna1^−/− mice before (black) and after (red) ear plugging procedure. C) Mean (±SEM) ABR thresholds for each tested frequency in Kcna1^+/+ (closed symbols, solid lines) and Kcna1^−/− mice (open symbols, broken lines) before (black) and after (red) ear plugging procedure. D) Both genotypes showed a 60-70% loss in threshold sensitivity.

Figure 2. Amplitudes of the acoustic startle reflex (ASR) are decreased in monaural wild types as well as in monaural and binaural Kcna1 mice

ASR amplitudes (squares and circles) and restless activity (ACT) scores (triangles) for Kcna1^+/+ (black symbols; n=19) and Kcna1^−/− mice (white symbols; n=12), with normal hearing (left) and with one ear plugged (right). All data are given as Mean (±SEM).

Figure 3. Kcna1^+/+ mice but not Kcna1^−/− mice benefit from binaural hearing in sound source discrimination tasks

A) For the spatial discrimination experiment, stimulus conditions illustrating the change of noise location from speaker 1 to speaker 2 at 20 ms before the startle eliciting stimulus (ES) that is presented at time point 0 s. B) PPI scores for Kcna1^+/+ (circles, n=17) and Kcna1^−/− mice (squares, n=12) with binaural (left) or monaural listening (right), with the test stimulus to the front of the mouse (cartoon), C) For the spatial discrimination experiment, same condition as in B except for the test stimulus presented to the side of the mouse (cartoon), PPI scores for Kcna1^+/+ (circles, n=17) and Kcna1^−/− mice (squares, n=12) with binaural (left) or monaural listening (right). All data are given as Mean (±SEM).

Figure 4. Kcna1^+/+ mice but not Kcna1^−/− mice benefit from binaural hearing in gap detection tasks

A) Stimulus condition showing the offset and onset of otherwise ongoing noise presented by one speaker to produce a 10 ms gap starting 60 ms before the ES at time point 0 s. B) PPI scores for the Kcna1^+/+ (circles, n=19) and the Kcna1^−/− mice (squares, n=12) with binaural (solid lines) and monaural listening (dashed lines, cartoon) for ISIs between noise offset and ES of 10 ms (left) and 60 ms (right). All data are given as Mean (±SEM).