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 basilar membrane 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 cell'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,Gadolin-ium.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 frequen-cies＞40 kHz.These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction,which does not require Prestin.

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

School of Life Sciences,Tsinghua University,Beijing 100084,China;IDG/McGovern Institute for Brain Research at Tsinghua University,Tsinghua University,Beijing 100084,China;Chinese Institute for Brain Research,Beijing 102206,China;School of Basic Medical Sciences,Capital Medical Univer-sity,Beijing 100069,China;Department of Otolaryngology,Head and Neck Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Ear Institute,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases,Shanghai 200011,China

神经科学通报（英文版）

[1]Jie Li;Shuang Liu;Chenmeng Song;Tong Zhu;Zhikai Zhao;Wenzhi Sun;Yi Wang;Lei Song;Wei Xiong-.Prestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice)[J].神经科学通报（英文版）,2022(07):769-784

Prestin,electromotility,stereociliary,Ca2+imaging,Gadolin,pharmacogenetic,frequen

Mediated,Frequency,Selectivity,Does,not,Cover,Ultrahigh,Frequencies,Mice,In,mammals,piezoelectric,protein,endows,outer,hair,cells,OHCs,eM,which,confers,capacity,change,cellular,length,response,alterations,membrane,potential,Together,basilar,resonance,possible,lays,foundation,enhancing,cochlear,sensitivity,frequency,selectivity,However,remains,debatable,whether,contributes,ultrahigh,hearing,due,intrinsic,nature,low,pass,features,property,mouse,that,magnitude,dissipates,within,bandwidth,human,speech,this,study,examined,role,sensing,broad,range,frequencies,kHz,mice,ultrasonic,vocalization,social,communication,audiometric,measurements,showed,ablation,did,Acoustic,associative,behavior,tests,confirmed,knockout,can,learn,sound,coupled,tasks,similar,control,Ex,vivo,experiments,demonstrated,without,still,exhibit,transduction,contrast,abolished,by,universal,channel,blocker,ium,salicylate,treatment,disrupts,By,manipulation,specific,largely,These,findings,are,target,support,does,require

0.50512