A linear, physiologically based, three-dimensional finite element model of the cochlea is developed. The model integrates the electrical, acoustic, and mechanical elements of the cochlea. In particular, the model includes interactions between structures in the organ of Corti (OoC), piezoelectric relations for outer hair cell (OHC) motility, hair bundle (HB) conductance that changes with HB deflection, current flow in the cross section and along the different scalae, and the feed-forward effect. The parameters in the model are based on guinea-pig data as far as possible. The model is vetted using a variety of experimental data on basilar membrane motion and data on voltages and currents in the OoC. Model predictions compare well, qualitatively and quantitatively, with experimental data on basilar membrane frequency response, impulse response, frequency glides, and scala tympani voltage. The close match of the model predictions with experimental data demonstrates the validity of the model for simulating cochlear response to acoustic input and for testing hypotheses of cochlear function. Analysis of the model and its results indicates that OHC somatic motility is capable of powering active amplification in the cochlea. At the same time, the model supports a possible synergistic role for HB motility in cochlear amplification.

Low-frequency hearing is critically important for speech and music perception, but no mechanical measurements have previously been available from inner ears with intact low-frequency parts. These regions of the cochlea may function in ways different from the extensively studied high-frequency regions, where the sensory outer hair cells produce force that greatly increases the soundevoked vibrations of the basilar membrane. We used laser interferometry in vitro and optical coherence tomography in vivo to study the low-frequency part of the guinea pig cochlea, and found that sound stimulation caused motion of a minimal portion of the basilar membrane. Outside the region of peak movement, an exponential decline in motion amplitude occurred across the basilar membrane. The moving region had different dependence on stimulus frequency than the vibrations measured near the mechanosensitive stereocilia. This behavior differs substantially from the behavior found in the extensively studied high-frequency regions of the cochlea.hearing | basilar membrane | optical coherence tomography | hair cells S ound causes traveling waves to propagate within the fluids of the inner ear and along the basilar membrane, from the base of the cochlea toward its apex (1-4). These waves move the sensory hair cells, deflect their stereocilia, and lead to receptor potential generation and modulation of spike rates in the auditory nerve. Because of systematic variations in basilar membrane properties, high-frequency sound stimulates sensory cells near the base of the cochlear spiral, whereas the low sound frequencies that are most important for speech and music perception cause maximal stimulation of hair cells near the apex of the spiral.Importantly, the sensory outer hair cells of the organ of Corti are mechanically active: Their soma changes length upon electrical stimulation (5, 6), and their hair bundles can provide force (7-9). Recent theoretical and experimental work showed that forces produced by the outer hair cells feed back into the sound-evoked motion of the basilar membrane and amplify the fluid motion associated with the traveling wave (10-12). The amplitude of the traveling wave therefore grows successively as it moves forward, causing a 1,000-fold increase of sound-evoked basilar membrane motion at the place of maximum vibration (13)-at least in the high-frequency regions of the cochlea. The functionally important low-frequency parts of the inner ear appear to behave in a different manner, however.Specifically, a recent mathematical model suggested a "ratchet" behavior, where the sensory outer hair cells amplify sound-evoked motion close to stereocilia, but not at the basilar membrane (14). If the theory has merit, basilar membrane movements are expected to be quite small, to be uninfluenced by hair-cell force generation, and to peak at a frequency that is unrelated to the frequency at which the hair bundles vibrate with their largest amplitude, a behavior distinct from the behavior found in the high-frequency regions.Some expe...

BackgroundMammalian hearing is refined by amplification of the sound-evoked vibration of the cochlear partition. This amplification is at least partly due to forces produced by protein motors residing in the cylindrical body of the outer hair cell. To transmit power to the cochlear partition, it is required that the outer hair cells dynamically change their length, in addition to generating force. These length changes, which have not previously been measured in vivo, must be correctly timed with the acoustic stimulus to produce amplification.Methodology/Principal FindingsUsing in vivo optical coherence tomography, we demonstrate that outer hair cells in living guinea pigs have length changes with unexpected timing and magnitudes that depend on the stimulus level in the sensitive cochlea.Conclusions/SignificanceThe level-dependent length change is a necessary condition for directly validating that power is expended by the active process presumed to underlie normal hearing.

To understand speech, the slowly varying outline, or envelope, of the acoustic stimulus is used to distinguish words. A small amount of information about the envelope is sufficient for speech recognition, but the mechanism used by the auditory system to extract the envelope is not known. Several different theories have been proposed, including envelope detection by auditory nerve dendrites as well as various mechanisms involving the sensory hair cells. We used recordings from human and animal inner ears to show that the dominant mechanism for envelope detection is distortion introduced by mechanoelectrical transduction channels. This electrical distortion, which is not apparent in the sound-evoked vibrations of the basilar membrane, tracks the envelope, excites the auditory nerve, and transmits information about the shape of the envelope to the brain.

The active amplification of sound-induced vibrations in the cochlea, known to be crucial for auditory sensitivity and frequency selectivity, is not well understood. The outer hair cell (OHC) somatic electromotility is a potential mechanism for such amplification. Its effectiveness in vivo is putatively limited by the electrical low-pass filtering of the cell's transmembrane potential. However, the transmembrane potential is an incomplete metric. We propose and estimate two metrics to evaluate the effectiveness of OHC electromotility in vivo. One metric is the OHC electromechanical ratio defined as the amplitude of the ratio of OHC displacement to the change in its transmembrane potential. The in vivo electromechanical ratio is derived from the recently measured in vivo displacements of the reticular lamina and the basilar membrane at the 19 kHz characteristic place in guinea pigs and using a model. The ratio, after accounting for the differences in OHC vibration in situ due to the impedances from the adjacent structures, is in agreement with the literature values of the in vitro electromechanical ratio measured by others. The second and more insightful metric is the OHC somatic power. Our analysis demonstrates that the organ of Corti is nearly optimized to receive maximum somatic power in vivo and that the estimated somatic power could account for the active amplification.

The detection of sound by the mammalian hearing organ involves a complex mechanical interplay among different cell types. The inner hair cells, which are the primary sensory receptors, are stimulated by the structural vibrations of the entire organ of Corti. The outer hair cells are thought to modulate these sound-evoked vibrations to enhance hearing sensitivity and frequency resolution, but it remains unclear whether other structures also contribute to frequency tuning. In the current study, sound-evoked vibrations were measured at the stereociliary side of inner and outer hair cells and their surrounding supporting cells, using optical coherence tomography interferometry in living anesthetized guinea pigs. Our measurements demonstrate the presence of multiple vibration modes as well as significant differences in frequency tuning and response phase among different cell types. In particular, the frequency tuning at the inner hair cells differs from other cell types, causing the locus of maximum inner hair cell activation to be shifted toward the apex of the cochlea compared with the outer hair cells. These observations show that additional processing and filtering of acoustic signals occur within the organ of Corti before inner hair cell excitation, representing a departure from established theories.

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Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions.