Investigating modulation of organ of Corti micromechanicsby outer hair cell electromotility

Hearing loss is one of the most prevalent health issues in the United States. The most common type is the sensorineural hearing loss which originates in the cochlea, the hearing organ in the inner ear. The cochlea encodes complex sounds into neural signals according to frequency components and pressure amplitudes. The cochlea contains three cavities filled with two distinct extracellular fluids – Na+ abundant perilymph and K+ abundant endolymph. The auditory sensory epithelium called the organ of Corti separates these two fluid spaces. The organ of Corti sits between the basilar membrane and the tectorial membrane, collectively called the organ of Corti complex. Vibrations in the organ of Corti complex modulate mechano-transduction currents of auditory mechano-receptor cells–the inner and the outer hair cells. While the inner hair cells are true auditory receptors in that they activate afferent nerves, the outer hair cells are reserved for other primary role. The outer hair cells generate mechanical force to amplify small sounds. Arguably, the identification of outer hair cells as the actuator for cochlear amplification is the greatest achievement in hearing research during past few decades. Despite progresses, there are incongruent explanations on how the outer hair cells operate for cochlear tuning and amplification. Insufficient knowledge regarding organ of Corti micro-mechanics is one of major obstacles. Recent studies are revealing that the organ of Corti vibrations are much more complicated than they were thought prior to the finding of outer hair cell motility. It is difficult to understand the interaction between passive vibration and somatic motility induced vibration from an in vivo preparation as they are interlinked. A new in vitro experimental approach was taken in this study to understand how outer hair cell motility modulates organ of Corti vibrations. In this study, the main experimental tool was the microchamber which restored the endolymph-perilymph separation of natural cochlea. Excised turn from the gerbil cochlea was placed and sealed between two chambers filled with the endolymph and perilymph, respectively. To maintain tissue viability including outer hair cell motility, appropriate fluid conditions were explored. Measurements were made from the middle turn of the gerbil cochlea because data from the middle turn are scarce. The experimental effort was complemented with two computational models. Both models consisted of three components–fluid mechanics of chamber or scala, organ of Corti micromechanics, electric circuit incorporating the mechano-transduction channels. One model represented our excised cochlear preparation, while the other model represented the intact cochlea. The former model helped to design and interpret experimental measurements, while the latter was to predict how organ of Corti micro-mechanics contribute to the systems-level responses. Our experimental approach is original in that mechanical and electrical stimulation were delivered…