Age-dependent Shifts in Spiral Ganglion Neuron Subtypes Are Associated with Interphase Gap-dependent Modulation of Electrically Evoked Compound Action Potentials in Mice

Older adults with profound hearing loss can derive substantial benefit from cochlear implants (CIs), yet outcomes are more variable than in younger recipients. Degeneration of spiral ganglion neurons (SGNs) is a major determinant of CI performance, and age-related hearing loss (ARHL) is accompanied by subtype-specific SGN alterations. However, how these changes shape electrically evoked neural responses remains unclear. This study examined the effects of age-related changes in SGN packing density and subtype composition on electrically evoked compound action potentials (ECAPs), with particular emphasis on interphase gap (IPG) sensitivity.

A cochlear implant model was established in 17 male C57BL/6 J mice across three age groups: 6–8-weeks, 6 months, and 12 months. ECAPs were quantified using absolute measures, including amplitude, slope, dynamic range, 50% level, and N1–P2 interpeak interval, as well as IPG effects. SGN packing density and subtype composition were assessed histologically, and their associations with ECAP measures were evaluated using correlation analyses.

Aging was associated with significant shifts in SGN subtype composition, characterized by a relative increase in Ia-type SGNs, along with robust IPG-related modulation of ECAP responses. ECAP measures showed differential associations with SGN packing density and subtype composition: IPG-sensitive measures such as amplitude, threshold and 50% level were primarily related to SGN packing density, whereas slope and dynamic range were more closely associated with Ia proportion. In addition, N1–P2 interpeak interval and its IPG effect showed strong correlations with both overall SGN packing density and Ia proportion, indicating sensitivity to both neural status and subtype balance.

Age-related changes in SGN packing density and subtype composition jointly influence ECAP characteristics and IPG sensitivity. Latency-based ECAP metrics appear particularly sensitive to underlying neural status and subtype balance. These findings provide new insight into the peripheral neural factors that may contribute to age-related variability in cochlear implant outcomes.