Cochlear amplification and tuning depend on the cellular arrangement within the organ of Corti

Abstract

The field of cochlear mechanics has been undergoing a revolution due to recent findings made possible by advancements in measurement techniques. While it has long been assumed that basilar-membrane (BM) motion is the most important determinant of sound transduction by the inner hair cells (IHCs), it turns out that other parts of the sensory epithelium closer to the IHCs, such as the reticular lamina (RL), move with significantly greater amplitude for weaker sounds. It has not been established how these findings are related to the complex cytoarchitecture of the organ of Corti between the BM and RL, which is composed of a lattice of asymmetric Y-shaped elements, each consisting of a basally slanted outer hair cell (OHC), an apically slanted phalangeal process (PhP), and a supporting Deiters' cell (DC). Here, a computational model of the mouse cochlea supports the hypothesis that the OHC micromotors require this Y-shaped geometry for their contribution to the exquisite sensitivity and frequency selectivity of the mammalian cochlea. By varying only the OHC gain parameter, the model can reproduce measurements of BM and RL gain and tuning for a variety of input sound levels. Malformations such as reversing the orientations of the OHCs and PhPs or removing the PhPs altogether greatly reduce the effectiveness of the OHC motors. These results imply that the DCs and PhPs must be properly accounted for in emerging OHC regeneration therapies.

Keywords: cochlea; cytoarchitecture; finite-element method; organ of Corti; regeneration.

Fig. 1.

Depictions of mouse cochlear anatomy (A–C) and corresponding structures in the FE model (D–G). (A) Reconstructed mouse inner ear from µCT imaging. The base and apex of the coiled cochlea are indicated along with the stapes at the oval window (OW). (B) A two-photon image of a radial cross section of the mouse scala media, with the OoC circled. (C) A longitudinal OoC cross-section showing the overlapping Y-shaped cytoarchitectural elements. A single element composed of a DC (gray), a basally oriented OHC (red), and an apically oriented PhP (blue) is outlined. The dimensions and longitudinal orientations of the Y-shaped elements vary along the BM length (10), as indicated by beam representations for sample apical (D) and basal (E) regions. (F) The FE model of the uncoiled mouse cochlea, spanning from base to apex, consisting of the scala vestibuli (including the scala-media) and scala tympani fluid chambers joined at the apical end by the helicotrema opening. Input sound passes through the OW and the round window (RW) is represented by a flexible membrane. The longitudinal, radial, and transverse directions correspond to the x, y, and z axes, respectively. (G) The fluid chambers are divided into near-field viscoacoustic domains (close to the RL and BM, taking viscosity of the fluid into account) and far-field acoustic domains (neglecting fluid viscosity). A single row of overlapping Y-shaped elements is sandwiched between the RL and BM in the model.

Fig. 2.

BM (A and C) and RL (B and D) vibration data from the cochlear base (A and B, 48 kHz; ref. 3) and apex (C and D, 10 kHz; ref. 2), measured in response to different input intensities (dashed lines), are compared against model results with different OHC gain-factor values α (solid lines). The model results were obtained on the BM and RL at the locations indicated by arrows. The model with α = 0 is compared with postmortem (PM) data. In the baseline model, each PhP spans across three OHCs, indicated by an inset in the top right of A.

Fig. 3.

Comparison of model vibration results between the baseline (dashed lines) and a version with flipped OHCs and PhPs (solid lines) for the BM (A and C) and RL (B and D) at the cochlear base (A and B) and apex (C and D). The BM and RL gains are reduced most dramatically at the apex. An inset in the top right of A shows the alteration of the Y-shaped elements by flipping the OHCs and PhPs. The Fig. 2 legend lists the corresponding α values.

Fig. 4.

Comparison of model vibration results between the baseline (dashed lines) and a version with deleted PhPs (solid lines) for the BM (A and C) and RL (B and D) at the cochlear base (A and B) and apex (C and D). In this case the BM and RL gains are reduced more significantly at the base. At the base the peaks do not shift to higher frequencies, whereas at the apex the peaks are very broad. An inset in A shows the alteration of the Y-shaped elements by deleting the PhPs. The Fig. 2 legend lists the corresponding α values.

Fig. 5.

The effects of the PhP span on the maximum gain (A and B) and ERB (C and D) of the BM (A and C) and RL (B and D) model vibrations. The lengths and angles of the PhPs are varied such that the number of OHCs that one PhP spans across varies from 1 to 10. The inset figures show the configuration of the Y-shaped elements for different Ns.