In mammals,the piezoelectric protein,Prestin,endows the outer hair cells(OHCs)with electromotility(eM),which confers the capacity to change cellular length in response to alterations in membrane potential.Together wit...In mammals,the piezoelectric protein,Prestin,endows the outer hair cells(OHCs)with electromotility(eM),which confers the capacity to change cellular length in response to alterations in membrane potential.Together with basilarmembrane resonance and possible stereociliary motility,Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity.However,it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cel's low-pass features.The low-pass_property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech.In this study,we examined the role of Prestin in sensing broad-range frequencies(4-80 kHz)in mice that use ultrasonic hearing and vocalization(to>100 kHz)for social communication.The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies>40 kHz.Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks,similar to control mice.Ex vivo cochlear Ca2+imaging experiments demonstrated that without Prestin,the OHCs still exhibit ultrahigh-frequency transduction,which in contrast,can be abolished by a universal cation channel blocker,Gadolinium.In vivo salicylate treatment disrupts hearing at frequencies<40 kHz but not ultrahigh-frequency hearing.By pharmacogenetic manipulation,we showed that specific ablation of the OHCs largely abolished hearing at frequencies>40 kHz.These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction,which does not require Prestin.展开更多
基金This work was supported by the National Natural Science Foundation of China(31522025,31571080,81873703,81770995,and 31861163003)Beijing Munic ipal Science and Technology Commission(Z181100001518001)+3 种基金a startup fund from the Tsinghua-Peking Centerfor Life Sciences to W.X.W.X.is a CIBR cooperative investigator(2020-NKX-XM-04)funded by the Open Collaborative Research Program of Chinese Institute for Brain ResearchNational Key Research and Development Project(2018YFC1003003)The Postdoctoral International Exchange Program(Talent-Introduction Program)the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300).
文摘In mammals,the piezoelectric protein,Prestin,endows the outer hair cells(OHCs)with electromotility(eM),which confers the capacity to change cellular length in response to alterations in membrane potential.Together with basilarmembrane resonance and possible stereociliary motility,Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity.However,it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cel's low-pass features.The low-pass_property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech.In this study,we examined the role of Prestin in sensing broad-range frequencies(4-80 kHz)in mice that use ultrasonic hearing and vocalization(to>100 kHz)for social communication.The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies>40 kHz.Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks,similar to control mice.Ex vivo cochlear Ca2+imaging experiments demonstrated that without Prestin,the OHCs still exhibit ultrahigh-frequency transduction,which in contrast,can be abolished by a universal cation channel blocker,Gadolinium.In vivo salicylate treatment disrupts hearing at frequencies<40 kHz but not ultrahigh-frequency hearing.By pharmacogenetic manipulation,we showed that specific ablation of the OHCs largely abolished hearing at frequencies>40 kHz.These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction,which does not require Prestin.
