Death of a spiral ganglion neuron: from synapses to the immune system

Sensorineural hearing loss is the most common hearing deficit and can be caused by damage to auditory neurons, the neurons that transmit information about sound from hair cells, the auditory receptor cells, to the brain. These neurons degenerate after various types of trauma to the cochlea, which may reduce the efficacy of cochlear implants that are used to restore hearing in individuals with lost or damaged hair cells. The exact causes of auditory neuron degeneration are unclear, but two common themes that could link hair cell loss with auditory neuron loss have emerged: damage to the synapses, or communication points, between hair cells and neurons, and immune/inflammatory response activation. In my thesis, I investigate these two ideas. First, I show that synapses are destroyed prior to loss of hair cells caused by aminoglycoside antibiotics, similar to damage caused by acoustic trauma. It is possible that this synapse loss is an initial trigger for the post-deafening immune response. Second, I show that both innate, or early and non-specific, and adaptive, or later and more targeted, immune responses are activated in the cochlea after deafening. However, my findings, along with comparisons to existing evidence from the literature, suggest that the innate and adaptive responses are playing different roles, with the adaptive response contributing directly to neurodegeneration after deafening. These findings contribute to our understanding of the neurodegenerative process in the cochlea, particularly that related to neuroinflammation, and will inform future studies on improving neuronal health and survival in the deafened cochlea.