Prestin links extrinsic tuning to neural excitation in the mammalian cochlea

Abstract

Hearing organs are usually distributed in tonotopic array from low to high frequencies and are very sensitively and sharply tuned to acoustic stimulation. Frequency tuning and tonotopicity of non-mammalian auditory hair cells is due largely to intrinsic properties of the hair cells [1], but frequency tuning and tonotopic organisation of the mammalian cochlea has an extrinsic basis in the basilar membrane (BM); a spiralling ribbon of collagen-rich extracellular matrix that decreases in stiffness from the high-frequency base of the cochlea to the low-frequency apex [2,3]. Sensitive frequency tuning is due to amplification, which specifically boosts low-level input to the mechanosensitive hair cells at their tonotopic location to overcome viscous damping [1-3]. In non-mammalian hearing organs, at least, amplification is attributed to calcium-mediated hair bundle motion [1]. In the mammalian cochlea, amplification is the remit of the sensory-motor outer hair cells (OHCs), located within the organ of Corti to exercise maximum mechanical effect on the motion of the BM and transmit cochlear responses to the adjacent sensory inner hair cells (IHCs) and, consequently, to the auditory nerve [1-3] (Figure 1A). OHCs behave like piezoelectric actuators, developing forces along their long axis in response to changes in membrane potential [2]. These forces are due to voltage-dependent conformational changes in the motor molecule prestin, which is densely distributed in the OHC lateral membranes [2]

Outer Hair Cells and Electromotility

“…The issue of possible changes in the mechanical properties of the OHCs can be circumvented by using a prestin mutant mouse where two residues are substituted near the presumed last transmembrane helix (V499G and Y501H), yielding OHCs that are structurally and biophysically near normal but have an NLC shifted very positively and outside the physiological operating range (Dallos et al 2008). In this mutant indeed, the basilar membrane is no longer sharply tuned and there is a reduction in both frequency selectivity and cochlear sensitivity, which are the major consequences with no assumed alterations in cochlear impedance matching (Weddell et al 2011).…”

Frequency-Dependent Properties of the Tectorial Membrane Facilitate Energy Transmission and Amplification in the Cochlea

“…Another consequence of this coupling is that the TM resonance can be reflected in other measurements (52). For example, the secondary maximum in sensitivity, observed at frequencies below the CF in BM frequency-tuning curves recorded in the extreme basal part of the mouse cochlea, is predicted to be due to the sharp TM resonance in the basal region of the cochlea (15,19,21,53,54).…”

Roles for Prestin in Harnessing the Basilar Membrane to the Organ of Corti

“…Mechanical impedance between the different elements of the cochlear partition must be matched optimally if energy is to be transferred effectively rather than dispersed. The key transfer of energy is between the OHCs and the BM on a strategically timed, cycle-by-cycle basis, as a feedback loop that underpins amplification and compression of cochlear responses (Mountain et al, 1983;Neely & Kim, 1983;Russell & Kössl, 1992;Nilsen & Russell, 1999;Robles & Ruggero, 2001) and the transfer of the net product of this process to the sensory IHCs (Chen et al, 2011;Fridberger et al, 2006;Mellado Lagarde et al, 2008;Nowotny & Gummer, 2006Richardson et al, 2008;Lukashkin et al, 2010;Weddell et al, 2011). The IHCs are located just above the attachment of the BM to the bony spiral lamina (Fig.…”

“…In vivo evidence in support of a dual role for prestin in the reciprocal coupling of the tuned vibrations of the BM to the organ of Corti and ultimately for auditory sensation (Weddell et al, 2011) was obtained from mice with mutations in the expression of prestin in the OHCs. Measurements were made from homozygous prestin knockout (KO) mice, with OHCs devoid of prestin (Mellado Lagarde et al, 2008), and homozygous prestin 499 knockin mice, with nonmotile prestin (Dallos et al, 2008), to test the hypothesis that prestin, acting as both a motile and structural element of OHCs, is essential for both power amplification (Lukashkin et al, 2007) and mechanical coupling of BM vibrations to the structures of the organ of Corti.…”

“…As a consequence of its proposed role in matching the acoustic impedance of the OHCs to that of the BM (Weddell et al, 2011), it is proposed that the cochleae of low-frequency specialists have become adapted to enable prestin to deliver isotonic electromotility to the compliant cochlea partition and the cochleae of high-frequency specialists facilitate the delivery of isometric forces against the stiff cochlear partition. Indeed, the specialized molecular structure of prestin of echolocating mammals ) may be modified for producing rapid forces by OHCs constrained in a relatively rigid framework.…”