Hearing impairment is a prevalent global health challenge, and cochlear implants (CIs) have emerged as a transformative solution for individuals with severe to profound hearing loss. However, the variability in CI outcomes, especially in complex listening situations, underscores the need for further advances in CI technology.

One major aspect of improved CI performance is a better understanding of spiral ganglion neurons (SGNs). CIs work by directly and electrically stimulating SGNs, thus their performance depends on healthy and excitable SGN populations. This thesis comprises a multifaceted approach aimed at improving CI performance by studying SGN behaviour at three different levels.

Firstly, this thesis investigates the intrinsic electrophysiological properties of SGNs at a single-cell level using a patch-clamp technique. Three distinct SGN classes based on their spike adaptation profiles have been identified and the interspike interval of action potentials in each class has been studied. Additionally, the changes in SGN response time or latencies across varying ranges of stimulation amplitudes have been evaluated.

Secondly, an in vitro gene therapy approach through the activation of the Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Delta (PIK3CD) gene has been investigated for its potential for SGN regeneration. This gene encodes for phosphoinositide 3-kinase (PI3K), a key initiator of the PI3K/Akt/mTOR pathway. The results of this therapy show enhanced neurite outgrowth and survival of SGNs. Furthermore, regenerated SGNs preserve their electrical activity and even possess enhanced excitability. This research establishes gene therapy as a promising avenue for SGN regeneration, offering potential benefits to CI users reliant on SGN viability and excitability.

Finally, this thesis pioneers the development of a cochlea-on-a-chip platform, designed to record population responses from SGNs in response to a real CI. This innovative platform supports SGN survival, replicates cochlear current spread dynamics and holds promise for a deeper understanding of CI-SGN interactions.

Collectively, this research helps us better understand SGN electrophysiology, explores SGN regeneration through gene therapy, and proposes a novel cochlea-on-a-chip platform, hereby potentially advancing CI technology and improving auditory experiences for those with hearing impairments.