1. Academic Validation
  2. Autophagy is Required for Remodeling in Postnatal Developing Ribbon Synapses of Cochlear Inner Hair Cells

Autophagy is Required for Remodeling in Postnatal Developing Ribbon Synapses of Cochlear Inner Hair Cells

  • Neuroscience. 2020 Apr 1;431:1-16. doi: 10.1016/j.neuroscience.2020.01.032.
Wei Xiong 1 Wei Wei 2 Yue Qi 1 Zhengde Du 1 Tengfei Qu 1 Ke Liu 3 Shusheng Gong 4
Affiliations

Affiliations

  • 1 Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
  • 2 Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
  • 3 Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address: liuke@ccmu.edu.cn.
  • 4 Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. Electronic address: gongss@ccmu.edu.cn.
Abstract

Cochlear ribbon synapses formed between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are immature at birth and they require dramatic morphological and functional developments to achieve auditory maturation in postnatal mice. However, the mechanism underlying this remodeling process of cochlear ribbon synapse remains elusive. Here, we report that Autophagy is necessary for the development and maturation of cochlear ribbon synapses in mice. In this study, significantly high levels of LC3B (a widespread marker of Autophagy) were found in the cochlea from postnatal day 1 (P1) to P15, which then decreased at P28 to P30. Treatment of mice at P7 with rapamycin or 3-methyladenine (activator and inhibitor of Autophagy, respectively) for 7 days led to the significant elevations of hearing threshold across frequencies from P15 to P30. Moreover, abnormal morphology of cochlear ribbon synapses and reduced IHC exocytosis function were detected from P15 to P30, which were likely associated to hearing impairment. Thus, our study demonstrated that Autophagy was required for remodeling of cochlear ribbon synapses and provided a new insight into autophagy-related hearing disorder during auditory development. Furthermore, we implicated a novel therapeutic target for sensorineural hearing loss.

Keywords

autophagy; exocytosis; postnatal; remodeling; ribbon synapse; sensorineural hearing loss.

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