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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.