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Peer-reviewedCC BY-NC-NDNature Communications

Molecularly defined auditory neuron subtypes show different vulnerabilities to noise- and age-related synaptopathy in mice

  • Joy A. Franco1,2,3
  • Taylor G. Copeland2,4,3
  • Ryan D. Merrow2,3
  • Lisa V. Goodrich5,3
5 affiliations
  1. 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA
  2. 2Department of Neurobiology, Harvard Medical School, Boston, MA, USA
  3. 3Harvard Medical School
  4. 4Speech and Hearing Bioscience and Technology PhD Program, Harvard University, Cambridge, MA, USA
  5. 5Department of Neurobiology, Harvard Medical School, Boston, MA, USA. [email protected]
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Abstract

Neuronal subtype-specific synaptopathy is a hallmark of many forms of neurodegeneration. We examined the cellular basis for synaptic vulnerability in the auditory system, where three subtypes of spiral ganglion neurons (SGNs)—Ia, Ib, and Ic—carry acoustic information from the cochlea to the brain. In response to noise and aging, a subset of synapses between inner hair cells and SGNs are lost, but it is unclear how this loss varies across SGN subtypes. Using genetic labelling, we showed that Ia SGNs have larger post-synaptic densities (PSDs) than Ib and Ic SGNs and are the most resilient subtype. Ia PSD volumes increased with age and were unchanged after noise exposure. By contrast, average Ib/Ic PSD volumes did not change with age but decreased with noise. Genetic reprogramming of Ib/Ic neurons to a Ia-like identity provided significant protection against noise-induced synaptopathy, linking identity to resilience and providing an entry point for therapeutics.

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Cite

BibTeXRIS
BibTeX
@article{franco2026molecularly,
  title = {{Molecularly defined auditory neuron subtypes show different vulnerabilities to noise- and age-related synaptopathy in mice}},
  author = {Joy A. Franco and Taylor G. Copeland and Ryan D. Merrow and Lisa V. Goodrich},
  journal = {Nature Communications},
  year = {2026},
  month = jul,
  doi = {10.1038/s41467-026-75275-3},
  url = {https://doi.org/10.1038/s41467-026-75275-3},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Molecularly defined auditory neuron subtypes show different vulnerabilities to noise- and age-related synaptopathy in mice
AU  - Joy A. Franco
AU  - Taylor G. Copeland
AU  - Ryan D. Merrow
AU  - Lisa V. Goodrich
PY  - 2026
DA  - 2026/07/10
JO  - Nature Communications
DO  - 10.1038/s41467-026-75275-3
UR  - https://doi.org/10.1038/s41467-026-75275-3
AB  - Neuronal subtype-specific synaptopathy is a hallmark of many forms of neurodegeneration. We examined the cellular basis for synaptic vulnerability in the auditory system, where three subtypes of spiral ganglion neurons (SGNs)—Ia, Ib, and Ic—carry acoustic information from the cochlea to the brain. In response to noise and aging, a subset of synapses between inner hair cells and SGNs are lost, but it is unclear how this loss varies across SGN subtypes. Using genetic labelling, we showed that Ia SGNs have larger post-synaptic densities (PSDs) than Ib and Ic SGNs and are the most resilient subtype. Ia PSD volumes increased with age and were unchanged after noise exposure. By contrast, average Ib/Ic PSD volumes did not change with age but decreased with noise. Genetic reprogramming of Ib/Ic neurons to a Ia-like identity provided significant protection against noise-induced synaptopathy, linking identity to resilience and providing an entry point for therapeutics.
SN  - 2041-1723
ER  -