Calculations of power flow in a cochlear model and measurements of inner-hair-cell stereocilia motion

The cochlea is an intricate biomechanical apparatus that converts the mechanical energy of sound into electrochemical energy in the auditory nerve fibers. The ability of mammals to distinguish different frequencies is attributed to the cochlea's ability to map specific sound frequencies onto different locations on the basilar membrane, a collagen-dense membrane extending along the length of the cochlea, like a mechanical Fourier transformer. The ability to hear an exceptionally large range of sound-pressure levels is attributed to the nonlinear-compressive amplification granted by the active processes in a live cochlea, which also sharpens the frequency resolution of hearing. The exact mechanisms by which these active processes give rise to amplification and the sharpening of frequency tuning remain elusive. It is known that the electromotile outer hair cells, located on top of the basilar membrane alongside the sensory inner hair cells, are an important part of the mechanical apparatus and the source of the active processes. Both types of hair cell feature specialized apical modifications called stereocilia, which are closely related to microvilli. The two cell types have distinct tasks. Upon pushing and pulling on the stereocilia of the inner hair cells, action potentials of the nerve fibers innervating the inner hair cells are triggered sending neural signals to the auditory cortex. On the other hand, for the outer hair cells, deflection of the stereocilia instead causes a change in the length of the cell body via a unique form of electromotility, which helps to accomplish cochlear amplification. The organ that houses the two types of hair cell, the organ of Corti, has a sophisticated structure that facilitates the transfer of motion between the basilar membrane, the stereocilia, and the outer hair cells. The exact mechanisms for the transfer of motion within the organ of Corti also remain unknown. It is hoped that this thesis will bring us closer to explaining the mechanism of cochlear amplification and stereocilia stimulation for the inner hair cells. Chapter 1 of this thesis introduces cochlear mechanics, the morphology and structural implications of the organ of Corti, the physiology of the hair cells, and what is known and unknown about cochlear amplification and stereocilia stimulation. Ever since the discovery of the outer-hair-cell electromotility, whether or not the outer hair cells actually generate energy to accomplish cochlear amplification has been heatedly debated. Chapter 2 addresses this question with a theoretical approach using a mouse cochlea model. The power output of the outer hair cells is directly calculated, and the common misconceptions around energy dissipation are clarified. The results show that the outer hair cells do provide power into the cochlea, on the order of a few fW, and contrary to what have been assumed, the power increases with sound-pressure level, so does the energy dissipated within the cochlea. Chapter 3 of this thesis aims to shine light on the mechanisms of stereocilia stimulation and their physiological relevance for the inner hair cells, by directly observing the inner-hair-cell stereocilia motion in situ using opened cochleae specimens from adult (P20-21) mice. The stereocilia motions were recorded using a high-speed camera at 12,500 frames per second, in response to a 2 or 3 kHz stimulation applied to the stapes, which is the middle-ear bone that transmits sound into the cochlea. Sub-pixel motions of individual stereocilia were extracted using a custom-designed algorithm. It is observed that the individual stereocilia within one bundle exhibit semi-independent motion. The magnitude and phase of the stereocilia motion relative to the organ of Corti are also valuable for understanding the stimulation mechanism and validating computational models.

Keywords: Mechanical Engineering.
Advisor: Steele Charles W.
Chaudhuri Ovijit 
Puria Sunil
Ricci Anthony