Prestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice  

作　　者：Jie Li Shuang Liu Chenmeng Song Tong Zhu Zhikai Zhao Wenzhi Sun Yi Wang Lei Song Wei Xiong 

机构地区：[1]School of Life Sciences,Tsinghua University,Beijing 100084,China [2]IDG/MeGovern Institute for Brain Research at Tsinghua University,Tsinghua University,Beijing 100084,China [3]Chinese Institute for Brain Research,Beijing 102206,China [4]School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China [5]Department of Otolaryngology,Head and Neck Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China [6]Ear Institute,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China [7]Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases,Shanghai 20001l,China

出　　处：《Neuroscience Bulletin》2022年第7期769-784,共16页神经科学通报（英文版）

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);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 Research;National 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).

摘　　要：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.

关 键 词：PRESTIN PIEZO2 Ultrahigh-frequency hearing ELECTROMOTILITY Outer hair cells 

分 类 号：R764[医药卫生—耳鼻咽喉科]