alpha-tectorin is an extracellular matrix molecule of the inner ear. Mice homozygous for a targeted deletion in a-tectorin have tectorial membranes that are detached from the cochlear epithelium and lack all noncollagenous matrix, but the architecture of the organ of Corti is otherwise normal. The basilar membranes of wild-type and alpha-tectorin mutant mice are tuned, but the alpha-tectorin mutants are 35 dB less sensitive. Basilar membrane responses of wild-type mice exhibit a second resonance, indicating that the tectorial membrane provides an inertial mass against which outer hair cells can exert forces. Cochlear microphonics recorded in alpha-tectorin mutants differ in both phase and symmetry relative to those of wild-type mice. Thus, the tectorial membrane ensures that outer hair cells can effectively respond to basilar membrane motion and that feedback is delivered with the appropriate gain and timing required for amplification.

Frequency tuning in the cochlea is determined by the passive mechanical properties of the basilar membrane and active feedback from the outer hair cells, sensory-effector cells that detect and amplify sound-induced basilar membrane motions. The sensory hair bundles of the outer hair cells are imbedded in the tectorial membrane, a sheet of extracellular matrix that overlies the cochlea’s sensory epithelium. The tectorial membrane contains radially-organised collagen fibrils imbedded in an unusual, striated-sheet matrix formed by two glycoproteins, Tecta and Tectb. In Tectb−/− mice the structure of the striated-sheet matrix is disrupted. Although these mice have a low-frequency hearing loss, basilar membrane and neural tuning are both significantly enhanced in the high-frequency regions of the cochlea, with little loss in sensitivity. These findings can be attributed to a reduction in the acting mass of the tectorial membrane, and reveal a novel role for this structure in controlling interaction along the cochlea.

Alpha-tectorin (encoded by Tecta) is a component of the tectorial membrane, an extracellular matrix of the cochlea. In humans, the Y1870C missense mutation in TECTA causes a 50- to 80-dB hearing loss. In transgenic mice with the Y1870C mutation in Tecta, the tectorial membrane's matrix structure is disrupted, and its adhesion zone is reduced in thickness. These abnormalities do not seriously influence the tectorial membrane's known role in ensuring that cochlear feedback is optimal, because the sensitivity and frequency tuning of the mechanical responses of the cochlea are little changed. However, neural thresholds are elevated, neural tuning is broadened, and a sharp decrease in sensitivity is seen at the tip of the neural tuning curve. Thus, using Tecta(Y1870C/+) mice, we have genetically isolated a second major role for the tectorial membrane in hearing: it enables the motion of the basilar membrane to optimally drive the inner hair cells at their best frequency.

The gene causative for the human nonsyndromic recessive form of deafness DFNB22 encodes otoancorin, a 120-kDa inner ear-specific protein that is expressed on the surface of the spiral limbus in the cochlea. Gene targeting in ES cells was used to create an EGFP knock-in, otoancorin KO (Otoa EGFP/EGFP ) mouse. In the Otoa EGFP/EGFP mouse, the tectorial membrane (TM), a ribbon-like strip of ECM that is normally anchored by one edge to the spiral limbus and lies over the organ of Corti, retains its general form, and remains in close proximity to the organ of Corti, but is detached from the limbal surface. Measurements of cochlear microphonic potentials, distortion product otoacoustic emissions, and basilar membrane motion indicate that the TM remains functionally attached to the electromotile, sensorimotor outer hair cells of the organ of Corti, and that the amplification and frequency tuning of the basilar membrane responses to sounds are almost normal. The compound action potential masker tuning curves, a measure of the tuning of the sensory inner hair cells, are also sharply tuned, but the thresholds of the compound action potentials, a measure of inner hair cell sensitivity, are significantly elevated. These results indicate that the hearing loss in patients with Otoa mutations is caused by a defect in inner hair cell stimulation, and reveal the limbal attachment of the TM plays a critical role in this process.T he sensory epithelium of the cochlea, the organ of Corti ( Fig. 1), contains two types of hair cell, the purely sensory inner hair cells (IHCs) and the electromotile, sensorimotor outer hair cells (OHCs). These cells are critically positioned between two strips of ECM, the basilar membrane (BM) and the tectorial membrane (TM). Signal processing in the cochlea is initiated when sound-induced changes in fluid pressure displace the BM in the transverse direction, causing radial shearing displacements between the surface of the organ of Corti (the reticular lamina) and the overlying TM (1). The radial shear is detected by the hair bundles of the IHCs and the OHCs (2), with the stereocilia of the OHC hair bundles forming an elastic link between the organ of Corti and the overlying TM (3). Deflection of the stereocilia gates the hair cell's mechanoelectrical transducer (MET) channels, thereby initiating a MET current (4) that promotes active mechanical force production by the OHCs, which, in turn, influences mechanical interactions between the TM and the BM (5, 6). This nonlinear frequency-dependent enhancement process, which boosts the sensitivity of cochlear responses to lowlevel sounds and compresses them at high levels, is known as the cochlear amplifier (7).Whereas the hair bundles of the OHCs are imbedded into the TM and therefore directly excited by relative displacement of the undersurface of the TM and the reticular lamina, those of the IHCs are not in direct contact with the TM, and the way in which they are driven by motion of the BM remains unclear. Intracellular recordings of the receptor potent...

The remarkable sensitivity, frequency selectivity, and dynamic range of the mammalian cochlea relies on longitudinal transmission of minuscule amounts of energy as passive, pressure-driven, basilar membrane (BM) traveling waves. These waves are actively amplified at frequency-specific locations by a mechanism that involves interaction between the BM and another extracellular matrix, the tectorial membrane (TM). From mechanical measurements of isolated segments of the TM, we made the important new (to our knowledge) discovery that the stiffness of the TM is reduced when it is mechanically stimulated at physiologically relevant magnitudes and at frequencies below their frequency place in the cochlea. The reduction in stiffness functionally uncouples the TM from the organ of Corti, thereby minimizing energy losses during passive traveling-wave propagation. Stiffening and decreased viscosity of the TM at high stimulus frequencies can potentially facilitate active amplification, especially in the high-frequency, basal turn, where energy loss due to internal friction within the TM is less than in the apex. This prediction is confirmed by neural recordings from several frequency regions of the cochlea.