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Updated: Oct 14, 2025
Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea
Published on: May 10, 2019
Macrophages Are Dispensable for Postnatal Pruning of the Cochlear Ribbon Synapses
Chaorong Yu1,2, Hui-Ming Gao1,2,3, Guoqiang Wan1,2,3,4
1MOE Key Laboratory of Model Animal for Disease Study, Department of Otorhinolaryngology-Head and Neck Surgery, The Affiliated Drum Tower Hospital of Medical School, Model Animal Research Center of Medical School, Nanjing University, Nanjing, China.
Abstract:
Ribbon synapses of cochlear hair cells undergo pruning and maturation before the hearing onset. In the central nervous system (CNS), synaptic pruning was mediated by microglia, the brain-resident macrophages, via activation of the complement system. Whether a similar mechanism regulates ribbon synapse pruning is currently unknown. In this study, we report that the densities of cochlear macrophages surrounding hair cells were highest at around P8, corresponding well to the completion of ribbon synaptic pruning by P8-P9. Surprisingly, using multiple genetic mouse models, we found that postnatal pruning of the ribbon synapses and auditory functions were unaffected by the knockout of the complement receptor 3 (CR3) or by ablations of macrophages expressing either LysM or Cx3cr1. Our results suggest that unlike microglia in the CNS, macrophages in the cochlea do not mediate pruning of the cochlear ribbon synapses.
Insights
Cochlear hair cell ribbon synapse pruning before hearing onset is not mediated by macrophages, unlike in the central nervous system. Macrophage ablation or complement receptor 3 knockout did not affect synapse pruning or auditory function.
Area of Science:
- Neuroscience
- Developmental Biology
- Auditory Science
Background:
- Ribbon synapses in cochlear hair cells mature before hearing onset.
- Microglia mediate synaptic pruning in the central nervous system (CNS) via complement system activation.
- The role of macrophages in cochlear ribbon synapse pruning remains unknown.
Purpose of the Study:
- To investigate whether cochlear macrophages mediate ribbon synapse pruning.
- To determine if the complement system is involved in this process.
Main Methods:
- Utilized genetic mouse models to ablate macrophages or disrupt complement signaling.
- Quantified cochlear macrophage density around hair cells.
- Assessed ribbon synapse pruning and auditory function postnatally.
Main Results:
- Cochlear macrophage density peaked around postnatal day 8, coinciding with ribbon synapse pruning completion.
- Genetic knockout of complement receptor 3 (CR3) or ablation of macrophages did not impair ribbon synapse pruning.
- Auditory function remained normal in knockout and ablated mice.
Conclusions:
- Cochlear macrophages do not appear to mediate ribbon synapse pruning.
- The mechanism of cochlear ribbon synapse pruning differs from that in the CNS.
- Complement system activation is likely not the primary driver of this process in the cochlea.
