Static length changes of cochlear outer hair cells can tune low-frequency hearing

The cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti. We develop a geometry-based kinematic model of the apical organ of Corti that reproduces salient, yet counter-intuitive features of the organ’s motion. Our analysis further uncovers a mechanism by which a static length change of the outer hair cells can sensitively tune the signal transmitted to the sensory inner hair cells. When the outer hair cells are in an elongated state, stimulation of inner hair cells is largely inhibited, whereas outer hair cell contraction leads to a substantial enhancement of sound-evoked motion near the hair bundles. This novel mechanism for regulating the sensitivity of the hearing organ applies to the low frequencies that are most important for the perception of speech and music. We suggest that the proposed mechanism might underlie frequency discrimination at low auditory frequencies, as well as our ability to selectively attend auditory signals in noisy surroundings

Cooperativity of Kv7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells.

The mammalian cochlea relies on active electromotility of outer hair cells (OHCs) to resolve sound frequencies. OHCs use ionic channels and somatic electromotility to achieve the process. It is unclear, though, how the kinetics of voltage-gated ionic channels operate to overcome extrinsic viscous drag on OHCs at high frequency. Here, we report ultrafast electromechanical gating of clustered Kv7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-Kv7.4 were revealed, using optogenetics strategies. Upon clustering, the half-activation voltage shifted negative, and the speed of activation increased relative to solitary channels. Clustering also rendered Kv7.4 channels mechanically sensitive, confirmed in consolidated Kv7.4 channels at the base of OHCs. Kv7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast Kv7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies

A Biophysical Model of the Role of the Outer Hair Cell in Cochlear Nonlinearity

It has been observed that the response characteristics of the basilar membrane in normal living cochleae are both frequency and level-sensitive (Robles & Ruggero 2001). The quality factor of the tuning curve is large at low sound levels and decreases as the sound level increases, and the peak of the tuning curve moves towards lower frequencies as the sound level increases. The current study proposes a nonlinear cochlear model that responds adaptively to the incoming sounds via feedback control arising from the mechanical attributes of the cochlear partition. These attributes are dependent on the membrane potential of the outer hair cells (He & Dallos 1999, Santos-Sacchi 1992). A parallel resistor-capacitor circuit analogy of the outer hair cell with related perilymph and endolymph potentials is designed to simulate sound-evoked changes in the outer hair cell membrane potential. Nonlinear responses of the cochlea, such as compression and two tone suppression, can be explained using this model. Furthermore, it has been shown that the basilar membrane response to pure tone stimuli is attenuated by directly stimulating the medial olivo-cochlear bundle using electrical shocks (Cooper & Guinan 2006). Basilar membrane responses in the presence of efferent stimulation can be demonstrated using the same model, through modulation of the outer hair cell rnembrane potential. The proposed model provides a unified account of the combined effect of sounds and efferent stimulation on cochlear responses

The sensitivity of the cochlear amplifier to changes in operating conditions

Frequency selectivity is one of the most important functions of the mammalian hearing organ – the cochlea. The interaction of fluid mass and organ of Corti compliance sets a traveling wave along the basilar membrane (BM), which is longitudinally tuned to different frequencies. Beyond this passive tuning process, cochlear amplification locally enhances the vibration of the best frequency peak by factors of hundreds to boost the frequency selectivity and sensitivity of the cochlea. This amplification is achieved by a positive feedback loop between BM motion and outer hair cell (OHC) electrical-mechanical response. However, this active mechanism is vulnerable to damage and cannot be fully recovered in vivo. As the instruments of cochlear amplification, the frequency response of BM and OHCs are of great importance to understand cochlear tuning process. This thesis used animal models, aimed to understand cochlear tuning and investigate possibilities to manipulate the cochlear amplifier, by testing the cochlear amplifier’s sensitivity to operating conditions. The first project tested whether the cochlear amplification can adjust to a lower endocochlear potential (EP), which controls OHC electromechanical force by providing part of the voltage source to drive OHC transduction current. To investigate this possibility, we use intraperitoneal (IP) and intravenous (IV) injection of furosemide to reversibly reduce EP, while monitoring the EP and cochlear amplification simultaneously. Cochlear amplification was monitored by measuring the local cochlear microphonic (LCM) and distortion product emission (DPOAE). With IV injection, the cochlear amplification observed in LCM could attain nearly full or even full recovery with reduced EP. This showed the cochlea has an ability to adjust to diminished operating condition. Furthermore, the cochlear amplifier and EP recovered with different time courses: cochlear amplification just started to recover after the EP was nearly fully recovered and stabilized. Using a Boltzmann model and the 2nd harmonic of the LCM to estimate the mechanoelectric transducer channel operating point, we found that the recovery of cochlear amplification occurred with re-centering of the operating point. The second project studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid, for better understanding cochlear fluid mechanics. Perilymphatic perfusion was applied with artificial perilymph and viscous sodium hyaluronate (Healon, HA) in four different concentrations. Using compound action potential (CAP) thresholds as an indicator of cochlear condition, our results and analysis indicated that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Histology of the cochleae perfused with higher shear stress showed the Reissner's membrane was torn. These data also indicated that the cochlea mechanics remains normal within increased perilymphatic fluid viscosity up to an increase of a factor of 50. Beside these findings, a temporary CAP threshold shift was observed, perhaps due to the presence and then clearance of viscous fluid within the cochlea, or to a temporary position shift of the organ of Corti. The last project was to test the effect of OHC intracellular Cl- concentration on cochlear amplification. Chloride is known to enable the electromotility of the OHC by binding its motor protein, prestin. By locally perfusing high chloride perilymph and the chloride ionophore tributyltin, this study investigated whether increasing intracellular chloride concentration can restore cochlear sensitivity in a cochlea that was slightly damaged. This had been shown by others in guinea pig. However, we did not observe recovery in several attempts in gerbil

Cochlea – A Physiological Description of a Finely Structured Sense Organ

The whole inner ear or the cochlea, responsible for hearing perception, represents a unique sense organ, including the organ of Corti and the inner ear endo- and perilymph. The fluid homeostasis of the lymph spaces with its parameters volume, concentration, osmolarity and pressure, as well as the finely aligned hair cell receptors, their supporting cells and structures embedded in these unique fluid spaces, corresponds to the specific necessities for adequate response to continuous stimulation and the outstanding discrimination capacity of the hearing system. The manuscript gives an overview and describes the structural characteristics and distinct physiological hearing qualities of the cochlea in comparison with the other human receptor cells and sense organs

Development of adaptive transducer based on biological sensory mechanism

textAn adaptive sensor concept and prototype has been developed based on a sensing element which is analogous to and inspired by the arrangement of outer hair cells and inner hair cells between the basilar membrane and tectorial membrane which form the organ of corti in mammalian cochlea. The bio-inspired design was supported by development of a bond graph model of the electromotility (active response) of outer hair cells. Outer hair cells perform like actuators and simulation results using this model are compared with physiological data found in the literature to verify its characteristic response. Insight gained from the model is used to develop a sensor structure analogous to the organ of corti and designed to measure acceleration. A piezoelectric bimorph was selected as the transducer basis, and a bond graph model of the bimorph in an accelerometer configuration was formulated to aid control design and simulation. There is no published data regarding the type of information transmitted among the inner hair cells, outer hair cells, and brain. Consequently, a controller intended to adjust the adaptation process similar to what might exist in the cochlear system has been developed for the sensor and based on a model referenced adaptive control algorithm. Simulations verify that the algorithm can successfully control and enhance performance of the sensor. Practicability of the design is evaluated by a series of experiments on a prototype. This study focused on using a controller structure that was programmed, implemented, and tested using programmable logic based on FPGA technology. The experiments evaluated how well the adaptive sensor could meet a specified performance requirement. Implementation issues that arise, such as the need for differentiators in the adaptive controller or internal propagation of vibration within the sensor structure, hinder the tuning ability. Nevertheless, the trends indicate that the algorithm can meet the desired performance if certain limitations can be overcome. Finally, recommendations have been made for expansion of the research in such fields as an alternative structure for tuning, sensor networking, and reference sensor configuration.Mechanical Engineerin

Update On Hearing Loss

Update on Hearing Loss encompasses both the theoretical background on the different forms of hearing loss and a detailed knowledge on state-of-the-art treatment for hearing loss, written for clinicians by specialists and researchers. Realizing the complexity of hearing loss has highlighted the importance of interdisciplinary research. Therefore, all the authors contributing to this book were chosen from many different specialties of medicine, including surgery, psychology, and neuroscience, and came from diverse areas of expertise, such as neurology, otolaryngology, psychiatry, and clinical and experimental audiology

Coupling and Elastic Loading Affect the Active Response by the Inner Ear Hair Cell Bundles

Active hair bundle motility has been proposed to underlie the amplification mechanism in the auditory endorgans of non-mammals and in the vestibular systems of all vertebrates, and to constitute a crucial component of cochlear amplification in mammals. We used semi-intact in vitro preparations of the bullfrog sacculus to study the effects of elastic mechanical loading on both natively coupled and freely oscillating hair bundles. For the latter, we attached glass fibers of different stiffness to the stereocilia and observed the induced changes in the spontaneous bundle movement. When driven with sinusoidal deflections, hair bundles displayed phase-locked response indicative of an Arnold Tongue, with the frequency selectivity highest at low amplitudes and decreasing under stronger stimulation. A striking broadening of the mode-locked response was seen with increasing stiffness of the load, until approximate impedance matching, where the phase-locked response remained flat over the physiological range of frequencies. When the otolithic membrane was left intact atop the preparation, the natural loading of the bundles likewise decreased their frequency selectivity with respect to that observed in freely oscillating bundles. To probe for signatures of the active process under natural loading and coupling conditions, we applied transient mechanical stimuli to the otolithic membrane. Following the pulses, the underlying bundles displayed active movement in the opposite direction, analogous to the twitches observed in individual cells. Tracking features in the otolithic membrane indicated that it moved in phase with the bundles. Hence, synchronous active motility evoked in the system of coupled hair bundles by external input is sufficient to displace large overlying structures