Aminoglycoside injury, but not genetic hair cell ablation, preferentially reduces Type Ic spiral ganglion neurons.

Spiral ganglion neurons (SGNs) are molecularly heterogeneous, and low-spontaneous-rate (Type Ic) SGNs are considered important for suprathreshold auditory processing, including encoding sounds in noisy environments. Preferential vulnerability of Type Ic SGNs has been reported in conditions in which primary neural injury is thought to play a major role, such as aging and noise exposure. However, it remains unclear whether preferential Type Ic vulnerability is shared across cochlear injury paradigms or varies with the nature of injury. Here, we investigated subtype-specific patterns of SGN degeneration using three cochlear injury models in adult mice: genetic hair cell-specific ablation in Pou4f3-diphtheria toxin receptor (DTR) mice, and local and acute systemic aminoglycoside injury models. In the DTR model, Type I SGNs underwent progressive degeneration without a detectable change in the proportion of Type Ic SGNs. In contrast, both aminoglycoside models showed significant reductions in Type I SGN density, accompanied by a decreased proportion of Type Ic SGNs, despite distinct patterns of hair cell injury between the local and acute systemic models. These findings demonstrate that distinct cochlear injury paradigms produce different patterns of SGN subtype vulnerability, suggesting that Type Ic vulnerability depends on the nature of cochlear injury.