PIEZO2 mediates ultrasonic hearing via cochlear outer hair cells in mice

Jie Li; Shuang Liu; Chenmeng Song; Qun Hu; Zhikai Zhao; Tuantuan Deng; Yi Wang; Tong Zhu; Linzhi Zou; Shufeng Wang; Jiaofeng Chen; Lian Liu; Hanqing Hou; Kexin Yuan; Hairong Zheng; Zhiyong Liu; Xiaowei Chen; Wenzhi Sun; Bailong Xiao; Wei Xiong

doi:10.1073/pnas.2101207118

PIEZO2 mediates ultrasonic hearing via cochlear outer hair cells in mice

Proc Natl Acad Sci U S A. 2021 Jul 13;118(28):e2101207118. doi: 10.1073/pnas.2101207118.

Authors

Jie Li^{1

2}, Shuang Liu^{1

2}, Chenmeng Song^{1

2}, Qun Hu^{1

2}, Zhikai Zhao^{1

2}, Tuantuan Deng^{2

3

4}, Yi Wang^{1

2}, Tong Zhu^{1

2}, Linzhi Zou^{1

2}, Shufeng Wang^{1

2}, Jiaofeng Chen^{1

2}, Lian Liu^{1

2}, Hanqing Hou^{1

2}, Kexin Yuan^{1

5}, Hairong Zheng⁶, Zhiyong Liu⁷, Xiaowei Chen^{8

9}, Wenzhi Sun^{10

11}, Bailong Xiao^{2

3

4}, Wei Xiong^{12

2}

Affiliations

¹ School of Life Sciences, Tsinghua University, Beijing, China 100084.
² IDG (International Data Group)/McGovern Institute for Brain Research at Tsinghua University, Tsinghua University, Beijing, China 100084.
³ School of Pharmaceutical Sciences, Tsinghua University, Beijing, China 100084.
⁴ Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China 100084.
⁵ Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China 100084.
⁶ Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Key Laboratory for MRI, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China 440305.
⁷ Institute of Neuroscience, CAS (Chinese Academy of Sciences) Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 200031.
⁸ Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, China 400038.
⁹ CAS (Chinese Academy of Sciences) Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 200031.
¹⁰ Chinese Institute for Brain Research, Beijing, China 102206.
¹¹ School of Basic Medical Sciences, Capital Medical University, Beijing, China 100069.
¹² School of Life Sciences, Tsinghua University, Beijing, China 100084; wei_xiong@tsinghua.edu.cn.

Abstract

Ultrasonic hearing and vocalization are the physiological mechanisms controlling echolocation used in hunting and navigation by microbats and bottleneck dolphins and for social communication by mice and rats. The molecular and cellular basis for ultrasonic hearing is as yet unknown. Here, we show that knockout of the mechanosensitive ion channel PIEZO2 in cochlea disrupts ultrasonic- but not low-frequency hearing in mice, as shown by audiometry and acoustically associative freezing behavior. Deletion of Piezo2 in outer hair cells (OHCs) specifically abolishes associative learning in mice during hearing exposure at ultrasonic frequencies. Ex vivo cochlear Ca²⁺ imaging has revealed that ultrasonic transduction requires both PIEZO2 and the hair-cell mechanotransduction channel. The present study demonstrates that OHCs serve as effector cells, combining with PIEZO2 as an essential molecule for ultrasonic hearing in mice.

Keywords: PIEZO2; hair cells; hearing; mechanotransduction; ultrasonic vocalization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism
Freezing Reaction, Cataleptic
Gene Deletion
HEK293 Cells
Hair Cells, Auditory, Outer / metabolism*
Hearing / physiology*
Humans
Ion Channels / metabolism*
Mechanotransduction, Cellular
Mice
Mice, Knockout
Ultrasonics*

Substances

Ion Channels
Piezo2 protein, mouse
Calcium