Back

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

Franco, J. A.; Copeland, T. G.; Merrow, R. D.; Goodrich, L.

2025-09-01 neuroscience
10.1101/2025.08.27.672747 bioRxiv
Show 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.

Published in Nature Communications (predicted rank #3) · training set

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.