A connexin30 mutation rescues hearing and reveals roles for gap junctions in cochlear amplification and micromechanics

Accelerated age-related hearing loss disrupts high-frequency hearing in inbred CD-1 mice. The p.Ala88Val (A88V) mutation in the gene coding for the gap-junction protein connexin30 (Cx30) protects the cochlear basal turn of adult CD-1Cx30A88V/A88V mice from degeneration and rescues hearing. Here we report that the passive compliance of the cochlear partition and active frequency tuning of the basilar membrane are enhanced in the cochleae of CD-1Cx30A88V/A88V compared to CBA/J mice with sensitive high-frequency hearing, suggesting that gap junctions contribute to passive cochlear mechanics and energy distribution in the active cochlea. Surprisingly, the endocochlear potential that drives mechanoelectrical transduction currents in outer hair cells and hence cochlear amplification is greatly reduced in CD-1Cx30A88V/A88V mice. Yet, the saturating amplitudes of cochlear microphonic potentials in CD-1Cx30A88V/A88V and CBA/J mice are comparable. Although not conclusive, these results are compatible with the proposal that transmembrane potentials, determined mainly by extracellular potentials, drive somatic electromotility of outer hair cells

Emilin 2 promotes the mechanical gradient of the cochlear basilar membrane and resolution of frequencies in sound

The detection of different frequencies in sound is accomplished with remarkable precision by the basilar membrane (BM), an elastic, ribbon-like structure with graded stiffness along the cochlear spiral. Sound stimulates a wave of displacement along the BM with maximal magnitude at precise, frequency-specific locations to excite neural signals that carry frequency information to the brain. Perceptual frequency discrimination requires fine resolution of this frequency map, but little is known of the intrinsic molecular features that demarcate the place of response on the BM. To investigate the role of BM microarchitecture in frequency discrimination, we deleted extracellular matrix protein emilin 2, which disturbed the filamentous organization in the BM. Emilin2-/- mice displayed broadened mechanical and neural frequency tuning with multiple response peaks that are shifted to lower frequencies than normal. Thus, emilin 2 confers a stiffness gradient on the BM that is critical for accurate frequency resolution

The Vestibular System Mediates Sensation of Low-Frequency Sounds in Mice

The mammalian inner ear contains sense organs responsible for detecting sound, gravity and linear acceleration, and angular acceleration. Of these organs, the cochlea is involved in hearing, while the sacculus and utriculus serve to detect linear acceleration. Recent evidence from birds and mammals, including humans, has shown that the sacculus, a hearing organ in many lower vertebrates, has retained some of its ancestral acoustic sensitivity. Here we provide not only more evidence for the retained acoustic sensitivity of the sacculus, but we also found that acoustic stimulation of the sacculus has behavioral significance in mammals. We show that the amplitude of an elicited auditory startle response is greater when the startle stimuli are presented simultaneously with a low-frequency masker, including masker tones that are outside the sensitivity range of the cochlea. Masker-enhanced auditory startle responses were also observed in otoconia-absent Nox3 mice, which lack otoconia but have no obvious cochlea pathology. However, masker enhancement was not observed in otoconia-absent Nox3 mice if the low-frequency masker tones were outside the sensitivity range of the cochlea. This last observation confirms that otoconial organs, most likely the sacculus, contribute to behavioral responses to low-frequency sounds in mice

Role of the tectorial membrane revealed by otoacoustic emissions recorded from wild-type and transgenic TectaENT/ENT mice

Distortion product otoacoustic emissions (DPOAE) were recorded from wild-type mice and mutant Tecta(deltaENT/deltaENT) mice with detached tectorial membranes (TM) under combined ketamine/xylaxine anesthesia. In Tecta(deltaENT/deltaENT) mice, DPOAEs could be detected above the noise floor only when the levels of the primary tones exceeded 65 dB SPL. DPOAE amplitude decreased with increasing frequency of the primaries in Tecta(deltaENT/deltaENT) mice. This was attributed to hair cell excitation via viscous coupling to the surrounding fluid and not by interaction with the TM as in the wild-type mice. Local minima and corresponding phase transitions in the DPOAE growth functions occurred at higher DPOAE levels in wild-type than in Tecta(deltaENT/deltaENT) mice. In less-sensitive Tecta(deltaENT/deltaENT) mice, the position of the local minima varied nonsystematically with frequency or no minima were observed. A bell-like dependence of the DPOAE amplitude on the ratio of the primaries was recorded in both wild-type and Tecta(deltaENT/deltaENT) mice. However, the pattern of this dependence was different in the wild-type and Tecta(deltaENT/deltaENT) mice, an indication that the bell-like shape of the DPOAE was produced by a combination of different mechanisms. A nonlinear low-frequency resonance, revealed by nonmonotonicity of the phase behavior, was seen in the wild-type but not in Tecta(deltaENT/deltaENT) mice