Notre capacité à communiquer et à apprécier la musique repose sur une discrimination de fréquences couvrant une large gamme de fréquences sonores. Cette propriété résulte de cellules mécanosensorielles « ciliées », qui sont réglées pour répondre de façon maximale à une fréquence caractéristique qui varie monotoniquement le long de l’axe de l’organe auditif, la cochlée. Les mécanismes cellulaires et moléculaires qui définissent la fréquence d’une cellule ciliée et régulent sa valeur pour différentes cellules afin de couvrir la gamme auditive demeurent néanmoins inconnus. Notre hypothèse de travail est que cette fréquence est réglée en partie par les propriétés mécaniques passives et actives de la « touffe ciliaire », l’antenne mécanosensorielle de la cellule ciliée. A l’aide d’une préparation excisée de la cochlée du rat, nous avons combiné l’iontophorèse de chélateurs de calcium (BAPTA ou EDTA) pour casser les liens de bout-de-cil qui connectent les stéréocils voisins de la touffe ciliaire, une stimulation grâce à un micro-jet de fluide pour estimer la raideur de la touffe ciliaire et des enregistrements en « patch-clamp » de courants de transduction afin de compter le nombre de liens de bout-de-cil intacts qui contribuent à la réponse. Avec les mouvements évoqués par la rupture des liens de bout-de-cil et avec nos mesures de raideur, nous avons pu estimer la tension dans toute la touffe ciliaire, ainsi que la tension dans un seul lien de bout-de-cil en connaissant le nombre de liens qui contribuent à cette tension. Dans les cellules ciliées externes, qui sont impliquées dans l’amplification du stimulus sonore mais qui n’envoient pas d’information neuronale au cerveau, nous avons observé un gradient de tension et de raideur lorsque la fréquence caractéristique de la cellule ciliée augmente, suggérant que ces paramètres physiques peuvent être impliqués dans le réglage d’une cellule ciliée à sa fréquence caractéristique. Au contraire, pour les cellules ciliées internes, les vraies cellules sensorielles de la cochlée, nos observations ne montrent pas de gradient significatif. De plus, nous avons observé des mouvements de la touffe ciliaire induits par la variation de la concentration en calcium, correspondant à une tension accrue pour des concentrations en calcium plus faibles. Ces mouvements sont similaires à ceux évoqués dans d’autres classes de vertébrés, tels que chez la grenouille ou chez la tortue. Ainsi, nos résultats réconcilient les expériences faites chez les vertébrés inférieurs et chez le mammifère, et montrent l’implication des gradients de la mécanique de la touffe ciliaire pour l’importante sélectivité fréquentielle de la cochlée / Our ability to communicate and appreciate music relies on acute frequency discrimination over a broad range of sound frequencies. This property results from the operation of mechanosensory “hair" cells, which are each tuned to respond maximally to a characteristic frequency that varies monotonically along the axis of the auditory organ, the cochlea. The cellular and molecular mechanisms that set the characteristic frequency of a hair cell and regulate its value among different cells to cover the auditory range have remained elusive. Our working hypothesis is that tuning results in part from passive and active mechanical properties of the “hair" bundle, the mechanosensory antenna of the hair cell.Using an excised preparation from the rat cochlea, we combined iontophoresis of a calcium chelator (BAPTA or EDTA) to break the tip links that interconnect neighbouring stereocilia of the hair-cell bundle, fluid-jet stimulation to estimate hair-bundle stiffness and patch-clamp recordings of transduction currents to count the number of intact transduction channels contributing to the response. From the movements evoked by tip-link breakage and our stiffness measurements, we were able to estimate tension in the whole hair bundle as well as, knowing the number of tip links contributing to this tension, in a single tip link.In outer hair cells, which are involved in sound amplification but do not send neural information to the brain, we observed a gradient of tension and stiffness from the low-frequency to the high-frequency end of the cochlea, suggesting that these physical parameters may help tune the hair cell to its characteristic frequency. Interestingly, with inner hair cells - the true sensors of the cochlea, our observations do not show any significant gradient. Furthermore, we observed calcium-evoked hair-bundle movements corresponding to an increased tension in the tip links at decreased concentrations of calcium. These movements were similar to those evoked in other classes of vertebrates, such as the frog or the turtle. Together, our results reconcile experiments performed in lower vertebrates with those performed in mammals and show the implication of hair-bundle mechanical gradients in the sharp frequency tuning of the cochlea

The mammalian cochlea has been the inspiration to develope contemporary cochlear implants and active dynamic sensors that operate in the sensor's resonance region and possess favorable nonlinear characteristics. In the present work, multi-channel and self-sensing active artificial hair cells (AHCs) made of piezoelectric cantilevers and controlled by a cubic damping feedback controller are developed numerically and experimentally. These novel AHCs function near a Hopf bifurcation and amplify or compress the output by a one-third power-law relationship with the input, analogous to the mammalian cochlear amplifier. The multi-channel AHCs have extended frequency bandwidth to sense over multiple resonant frequencies, unlike conventional single-channel AHCs. Therefore, the adoption of these AHCs reduces the number of required sensors to cover the desired bandwidth of interest in an array format. Furthermore, a novel self-sensing active AHC is created in this study using quadmorph beams for future cochlear implants or sensor design applications. The self-sensing scheme allows miniaturization of the system, embedding AHCs in a limited space, and fabrication of AHC arrays by omitting external sensors from the system for practical implementation. Preliminary research on the extension of this research to MEMS AHCs and arrays of AHCs is also presented. The active AHCs can lead to transformative improvements in the dynamic range, sharpness of the response, and threshold of sound detection in cochlear implants to aid individuals with sensorineural hearing loss. Additionally, they can enhance the dynamic properties of sensors such as fluid flow sensors, microphones, and vibration sensors for various applications. / Doctor of Philosophy / In the mammalian auditory system, the acoustic wave that enters the ear canal is transmitted to the cochlea of the inner ear where it is decomposed into its frequency components. The cochlea then amplifies faint sounds and compresses high-level signals and as these processes stop due to damage, severe hearing loss occurs. Therefore, the present work is focused on developing artificial hair cells (AHCs) that can accurately replicate cochlea's behavior and aid the creation of prostheses for hearing restoration. In this work, the AHC is a beam with piezoelectric layers that is integrated with a control system designed to apply the cochlea-like amplification/compression on the beam. Experimental and simulation results show that the AHC is able to amplify or compress the output based on its input level similar to the mammalian cochlea. In contrast to previous designs of AHCs where each AHC could sense a single frequency, the system developed in this work possesses multiple sensing channels to increase the frequency range of the AHC. Furthermore, the development of a novel self-sensing scheme allows the omission of the external sensor that was required for the AHC operation in previous devices. This advancement in the self-sensing AHC design paves the way for creating fully implantable AHCs to replace the damaged parts of the cochlea. These multi-channel self-sensing AHCs have the potential to be used in the creation of cochlear implants, or sensors such as accelerometers, microphones, and hydrophones with improved dynamic properties. AHCs with different lengths, i.e. different sensing frequencies, can be mounted in an array format to cover the speech frequency range for speech recognition in individuals with hearing loss.

The cochlea is known to exhibit a nonlinear, mechanical amplification which allows the ear to detect faint sounds, improves frequency discrimination, and broadens the range of sound pressure levels that can be detected. In this work, active artificial hair cells (AHC) are proposed and developed which mimic the nonlinear cochlear amplifier. Active AHCs can be used to transduce sound pressures, fluid flow, accelerations, or another form of dynamic input. These nonlinear sensors consist of piezoelectric cantilever beams which utilize various feedback control laws inspired by the living cochlea. A phenomenological control law is first examined which exhibits similar behavior as the living cochlea. Two sets of physiological models are also examined: one set based on outer hair cell somatic motility and the other set inspired by active hair bundle motility. Compared to passive AHCs, simulation and experimental results for active AHCs show an amplified response due to small stimuli, a sharpened resonance peak, and a compressive nonlinearity between response amplitude and input level. These bio-inspired devices could lead to new sensors with lower thresholds of sound or vibration detection, improved frequency sensitivities, and the ability to detect a wider range of input levels. These bio-inspired, active sensors lay the foundation for a new generation of sensors for acoustic, fluid flow, or vibration sensing. / Ph. D.

The human sense of hearing is characterized by its exquisite sensitivity, sharp frequency selectivity, and wide dynamic range. These features depend on an active process that in the inner ear boosts vibrations evoked by auditory stimuli. Spontaneous otoacoustic emissions constitute a demonstrative manifestation of this physiologically vulnerable mechanism. In the cochlea, sensory hair bundles transduce sound-induced vibrations into neural signals. Hair bundles can power mechanical movements of their tip, oscillate spontaneously, and operate as tuned nonlinear amplifiers of weak periodic stimuli. Active hair-bundle motility constitutes a promising candidate with respect to the biophysical implementation of the active process underlying human hearing. The responsiveness of isolated hair bundles, however, is seriously hampered by intrinsic fluctuations. In this thesis, we present theoretical and experimental results concerning the noise-imposed limitations of nonlinear amplification by active sensory hair bundles. We analyze the effect of noise within the framework of a stochastic description of hair-bundle dynamics and relate our findings to generic aspects of the stochastic dynamics of oscillatory systems. Hair bundles in vivo are often elastically coupled by overlying gelatinous membranes. In addition to theoretical results concerning the dynamics of elastically coupled hair bundles, we report on an experimental study. We have interfaced dynamic force clamp performed on a hair bundle from the sacculus of the bullfrog with real-time stochastic simulations of hair-bundle dynamics. By means of this setup, we could couple a hair bundle to two virtual neighbors, called cyber clones. Our theoretical and experimental work shows that elastic coupling leads to an effective noise reduction. Coupled hair bundles exhibit an increased coherence of spontaneous oscillations and an enhanced amplification gain. We therefore argue that elastic coupling by overlying membranes constitutes a morphological specialization for reducing the detrimental effect of intrinsic fluctuations.

The human sense of hearing is characterized by its exquisite sensitivity, sharp frequency selectivity, and wide dynamic range. These features depend on an active process that in the inner ear boosts vibrations evoked by auditory stimuli. Spontaneous otoacoustic emissions constitute a demonstrative manifestation of this physiologically vulnerable mechanism. In the cochlea, sensory hair bundles transduce sound-induced vibrations into neural signals. Hair bundles can power mechanical movements of their tip, oscillate spontaneously, and operate as tuned nonlinear amplifiers of weak periodic stimuli. Active hair-bundle motility constitutes a promising candidate with respect to the biophysical implementation of the active process underlying human hearing. The responsiveness of isolated hair bundles, however, is seriously hampered by intrinsic fluctuations. In this thesis, we present theoretical and experimental results concerning the noise-imposed limitations of nonlinear amplification by active sensory hair bundles. We analyze the effect of noise within the framework of a stochastic description of hair-bundle dynamics and relate our findings to generic aspects of the stochastic dynamics of oscillatory systems. Hair bundles in vivo are often elastically coupled by overlying gelatinous membranes. In addition to theoretical results concerning the dynamics of elastically coupled hair bundles, we report on an experimental study. We have interfaced dynamic force clamp performed on a hair bundle from the sacculus of the bullfrog with real-time stochastic simulations of hair-bundle dynamics. By means of this setup, we could couple a hair bundle to two virtual neighbors, called cyber clones. Our theoretical and experimental work shows that elastic coupling leads to an effective noise reduction. Coupled hair bundles exhibit an increased coherence of spontaneous oscillations and an enhanced amplification gain. We therefore argue that elastic coupling by overlying membranes constitutes a morphological specialization for reducing the detrimental effect of intrinsic fluctuations.