ohc somatic

Outer hair cell somatic, not hair bundle, motility is the basis of the cochlear amplifier Marcia M Mellado Lagarde 1,2 , Markus Drexl 1,2 , Victoria A Lukashkina 1 , Andrei N Lukashkin 1 & Ian J Russell 1 Sensitivity, dynamic range and frequency tuning of the cochlea are attributed to amplification involving outer hair cell stereocilia and/or somatic motility. We measured acoustically and electrically elicited basilar membrane displacements from the cochleae of wild-type and Tecta DENT/ DENT mice, in which stereocilia are unable to contribute to amplification near threshold. Electrically elicited responses from Tecta DENT/ DENT mice were markedly similar to acoustically and electrically elicited responses from wild-type mice. We conclude that somatic, and not stereocilia, motility is the basis of cochlear amplification. Mec hanoe lectri cal sensory transdu ction in the mamma lian cochl ea takes place in the organ of Corti, which is sandwiched between the basilar and tectorial membranes (Fig. 1a). Sensory transduction is initia ted when sound-ind uced vibrations of the basilar membrane deflect the hair bundles of stereocilia at the apical poles of the outer hair cells (OHCs), gating the mechanosensitive transducer channels at their tips 1 . Deflection occurs through radial shear between the reticular lamina and the tectorial membrane to which the hair bundles project. The resulting flow of current into the sensory-motor OHCs initiates activ e mechanica l forc es that amplif y l ow-l evel and compres s high-le vel basilar membrane displacements 2 . Amplification is frequency dependent, and, for every location in the cochlea, effective amplification occurs around the characteristic frequency to which the location is tuned, thus providing the exquisite sensitivity and enormous dynamic range of the cochlea 3,4 . Two mechanisms have been suggested to function as the cochlear amp lifi er . One is vol tag e-d epe nd ent somaticmotili ty res ulti ng fro m the activity of the motor protein prestin in the OHC lateral membranes 1 . The other relies on hair-bundle motility driven by calcium currents 1 . The pr estin motor is uniq ue to OHCs of the ma mma lia n coch lea and is essenti al for cochlear frequency tuning and sensiti vity 1 . Prestin, however, has not been shown to be the unequivocal source of cochlear amplification 1 . Calcium-dependent hair-bundle motility is a ubiqui- tous featur e of hair cells 1 , but only in vitro studies have predicted that it is the source of amplification in the mammalian cochlea 5,6 . Here, we investigate the involvement of hair-bundle and somatic mot ili ty in the amp lifi cat ion and tuni ng of basi lar mem bra ne res pons es to acoustic and ele ctri cal coc hlea r stim ulat ion in wil d-ty pe Tecta +/+ and mutant Tecta DENT/ DENT mice 7 . The OHC hair bundles of Tecta +/+ mice are cou ple d mec han ica lly to the tec tor ial mem bra ne, but thos e of Tecta DENT/ DENT mic e are freest and ing and are not atta che d to the tectorial membrane, which is vestigial and is not associated with the organ of Corti in Tecta DENT/ DENT mice 7 . Basilar membrane responses to acoustic cochlear stimulation depend on sensory transduction that is mediated via displacem ents of the OHC hair bundles. The hair bundles of Tecta +/+ mice are displaced through interaction with the tectorial membra ne, whe rea s tho se of Tecta DENT/ DENT mic e are dis pla cedby fluid flow when basilar membrane velocity is sufficiently large 7 . Electrical stimulation of the cochlea bypasses sensory transduction 8 and directly drives both OHC somatic and hair-bundle motility 1,5,6 . In Tecta +/+ mice, however, the presence of the tectorial membrane will permit ele ctr ica lly eli cit ed hai r- bun dle mo vem ents to inte rac t wit h the tect ori al membrane, an opportunity that is precluded to the hair bundles of Tecta DENT/ DENT mice 7 . By exploiting the differences between Tecta +/+ and Tecta DENT/ DENT mice in hair -bundle tectorial membrane interaction, we were able to conclude that somatic, and not hair-bundle, mot ili ty is the basis of coc hlea r amplifi cati on for nea r-t hre sho ld displacements of the basilar membrane. We measured the frequency tuning, sensitivity and gain (amplification ) of acou stica lly elici ted basi lar membrane displac eme nts in the basal, high-frequency turn of the cochleae of Tecta +/+ mice (Supple- mentary Methods online). These measurements were compared with those taken from Tecta DENT/ DENT mice, which lack a functional tectorial membrane, and with those from the electrically elicited basilar membrane responses from both Tecta +/+ and Tecta DENT/ DENT mice described below. In response to tones at the characteristic frequency of the basilar membrane location, the dependen ce of basilar membrane displacement on sound pressure level (SPL) for Tecta +/+ mice was more nonlinear, compre ssiv e and sensi tive than that meas ured from Tecta DENT/ DENT mice 7 (Fig. 1b). Threshold frequency-tuning curves, where the sound pressure required to elicit a basilar membrane threshold displacement is plotted as a fun cti on of fre que ncy ( Fig . 1c,d and Supplementary Fig. 1 online), showed that those of Tecta DENT/ DENT mice were about 25 dB les s sen sit iv e at the ch aracteris ticfrequ enc y and ha d mu ch br oad er tuning with a smaller Q 10dB (ratio of the characteristic frequency to the bandwidth measured 10 dB from the tip) 7 than the basilar membrane tuning curves from Tecta +/+ mice (Table 1). The tuning curves had additional threshold minima below the characteristic frequency. One of these at R1 (B0.6 octaves below the characteristic frequency; Table 1) has been described previously and is attributed to the resonance of the tectorial membrane 7 . It was present, therefore, in tuning curves from Tecta +/+ , but not Tecta DENT/ DENT , mi ce. The oth er min imum at R2 (B0.3 octaves below the characteristic frequency; Table 1), which is apparent in the tuning curve s of both Tecta +/+ and Tecta DENT/ DENT mice, is recognized here for the first time, to the best of our knowledge, Received 5 February; accepted 28 April; published online 30 May 2008; doi:10.1038/nn.2129 1 School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK. 2 These authors contributed equally to this work. Correspondence should be addressed to I.J.R. ([email protected]). 74 6 VOLUME 11 [ NUMBER 7 [ JULY 2008 NATURE NEUROSCIENCE BRIEF COMMUNICATIONS

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