Prestin's role in cochlear frequency tuning and transmission of mechanical responses to neural excitation

The remarkable power amplifier [1] of the cochlea boostslow-level and compresses high-level vibrations of the basilarmembrane (BM) [2]. By contributing maximally at the characteristicfrequency (CF) of each point along its length, theamplifier ensures the exquisite sensitivity, narrow frequencytuning, and enormous dynamic range of the mammaliancochlea. The motor protein prestin in the outer hair cell (OHC)lateral membrane is a prime candidate for the cochlearpower amplifier [3]. The other contender for this role is theubiquitous calcium-mediated motility of the hair cell stereocilia,which has been demonstrated in vitro and is based onfast adaptation of the mechanoelectrical transduction channels[4, 5]. Absence of prestin [6] from OHCs results in a40–60 dB reduction in cochlear neural sensitivity [7]. Herewe show that sound-evoked BM vibrations in the high-frequencyregion of prestin2/2 mice cochleae are, surprisingly,as sensitive as those of their prestin+/+ siblings. The BMvibrations of prestin2/2 mice are, however, broadly tunedto a frequency approximately a half octave below the CF ofprestin+/+ mice at similar BM locations. The peak sensitivityof prestin+/+ BM tuning curves matches the neural thresholds.In contrast, prestin2/2 BM tuning curves at their bestfrequency are >50 dB more sensitive than the neural responses.We propose that the absence of prestin from OHCs,and consequent reduction in stiffness of the cochlea partition,changes the passive impedance of the BM at highfrequencies, including the CF. We conclude that prestin influencesthe cochlear partition’s dynamic properties thatpermit transmission of its vibrations into neural excitation.Prestin is crucial for defining sharp and sensitive cochlearfrequency tuning by reducing the sensitivity of the lowfrequencytail of the tuning curve, although this necessitatesa cochlear amplifier to determine the narrowly tuned tip