Cochlear neural functional competence: an integrative transcriptomic module analysis of excitability, plasticity and...

Area of Science:

• Neuroscience
• Genomics
• Otolaryngology

Background:

• Cochlear implants (CIs) stimulate spiral ganglion neurons (SGNs) but auditory outcomes vary.
• SGN survival alone doesn't fully predict CI performance.
• Transcriptional programs in SGNs related to excitability, plasticity, and injury may better reflect neural function.

Purpose of the Study:

• To develop and validate a transcriptomic framework, the Cochlear Neural Functional Competence (CNFC) score, for assessing SGN functional state.
• To analyze cochlear transcriptomic data across development, adulthood, and injury models.
• To correlate CNFC with neuronal survival and functional outcomes.

Main Methods:

• Re-analysis of public cochlear transcriptomic datasets (RNA-seq, microarrays) from development, adulthood, noise-induced hearing loss (NIHL), and deafening models.
• Assembly of gene modules for excitability, plasticity, trophic support, and injury/inflammation.
• Quantification of module activity using within-dataset standardized scores.
• Derivation and validation of the CNFC score (Excitability + Trophic - Injury) using a minimal 24-gene panel.

Main Results:

• Developmental maturation showed increased excitability transcripts and decreased cytoskeletal components.
• Adult hair cells exhibited distinct trophic signatures.
• In NIHL models, MSC therapy altered excitability and inflammation transcripts.
• CNFC decreased in spiral ganglion regions after noise exposure and in deafened spiral ganglion.
• The 24-gene CNFC panel showed high correlation with full-module scoring.

Conclusions:

• CNFC provides a transparent, hypothesis-generating framework for assessing cochlear neuronal functional state from transcriptomic data.
• This score complements traditional neuronal survival metrics.
• CNFC facilitates cross-study integration and identifies candidate programs for mechanistic investigation.