ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Non-Neuronal Cells
Cochlear neural functional competence: an integrative transcriptomic module analysis of excitability, plasticity and microenvironmental support programs
Provisionally accepted
- The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Background: Cochlear implants (CIs) restore hearing by directly stimulating spiral ganglion neurons (SGNs), yet auditory outcomes remain highly variable. Increasing evidence suggests that SGN survival alone incompletely predicts CI performance; instead, transcriptional programmes governing neuronal excitability/synaptic transmission, structural plasticity, trophic–metabolic support and injury/inflammation may better reflect neural functional competence. Methods: We re-analysed publicly available cochlear transcriptomic datasets spanning development, adulthood and injury/degeneration. Primary resources included developmental FACS RNA-seq of hair cells and surrounding tissue, adult inner-and outer-hair-cell microarrays, and a noise-induced hearing loss (NIHL) RNA-seq cohort following mesenchymal stromal cell (MSC) therapy. We additionally analysed independent injury/degeneration datasets, including spatial transcriptomics of spiral ganglion regions after noise exposure and spiral ganglion RNA-seq after aminoglycoside-induced deafening. Guided by cochlear neuroscience literature and functional enrichment, we assembled gene modules for excitability, plasticity, trophic/metabolic support and injury/inflammation. Module activity was quantified using within-dataset standardized scores from normalized expression, avoiding cross-platform merging. We derived a Cochlear Neural Functional Competence (CNFC) score (Excitability + Trophic − Injury) and assessed robustness using a minimal 24-gene panel. External validation was performed in an independent purified SGN dataset, and CNFC was benchmarked against transcriptome-wide principal components. Results: Developmental maturation was characterized by increasing excitability-associated transcripts alongside down-regulation of actin/cytoskeletal remodelling components. Adult hair cells displayed distinct trophic signatures. In the NIHL model, MSC therapy was associated with transcriptional suppression of excitatory receptor and channel genes, consistent with a shift in the injury/inflammation–excitability balance, although functional consequences remain to be established. Importantly, in independent injury/degeneration datasets, CNFC decreased in spiral ganglion neuronal regions after noise exposure and in deafened spiral ganglion. Across datasets, CNFC captured coherent trends and remained highly correlated with full-module scoring when reduced to the 24-gene panel. Conclusions: CNFC is a transparent, hypothesis-generating framework for summarizing cochlear neuronal functional state from transcriptomic data, complementing traditional survival metrics. By prioritizing interpretable modules and standardized within-dataset scoring, CNFC supports cross-study integration and highlights candidate programmes for mechanistic testing.
Keywords: cochlear implant, cytoskeletal plasticity, gene-module scoring, Hearing Loss, Mesenchymal Stromal Cells, Neural excitability, neurotrophin support, noise-induced hearing loss
Received: 28 Dec 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Guo, Wang, Gao, Feng, Wu, Ren and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Li Guo
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