The Use of Primary Spiral Ganglion Cells in Studying Glutamate Receptor Function and Excitotoxicity in the Cochlea

Sensorineural hearing loss (SNHL) is caused by excessive noise exposure, ototoxic drugs, and aging. SNHL is frequently linked to glutamate excitotoxicity, as glutamate is the main excitatory neurotransmitter at the inner hair cell – spiral ganglion neuron synapses. However, we still do not fully understand the specific roles of different glutamate receptor subtypes both in normal signaling and in causing excitotoxic damage. The investigation of these questions demands the availability of relevant experimental models. This review aims to compare existing protocols for obtaining primary spiral ganglion neurons in vitro and to assess the utility of this model in studying glutamatergic transmission. A literature search in PubMed and Google Scholar identified 16 relevant articles in English published since 1990, when the model was first introduced. Our analysis reveals significant heterogeneity protocols in isolation and conditions of cultivation. We highlight the significant differences in glutamate concentrations when modeling excitotoxicity and the glutamate receptor agonists used to study electrophysiological properties. The most significant limitation of this model is the loss of the native microenvironment of neurons, including their dendritic and axonal contacts. Nevertheless, primary spiral ganglion neurons serve as a suitable in vitro model for investigating auditory neuron function and pathology. This in vitro model allows detailed study of the mechanisms underlying ototoxicity and otoprotection. The number of neurons and neurite length serve as reliable indicators of otoprotective effects under conditions of glutamate excitotoxicity. This work may help researchers who plan to use the primary SGNs in their laboratories, as well as those who aim to optimize their methods based on accumulated experience.