The remarkable ability of the auditory system to accurately transduce acoustic signals from the environment into electrical signals in the brain is the product of finely tuned developmental and functional pathways. Before the onset of hearing, cochlear inner hair cells undergo a series of developmental steps, which involve changes to their biophysical and molecular properties.
One of these developmental steps, called spontaneous activity is driven by stimulus-independent action potentials, generated by immature hair cells in the prehearing stage of the mammalian cochlea. Spontaneous activity is calcium-dependent and generates rhythmic waves in levels of intracellular calcium within the organ of Corti (Kros et al., 1998; Johnson et al., 2017a). Similar to its role in other sensory systems (such as the visual system; Fisher, 1979; Soto et al., 2012), spontaneous activity in the cochlear inner hair cells serves to develop the ribbon synapse, refine afferent circuits (Johnson et al., 2013; Clause et al., 2014) and influence neuronal survival (Zhang-Hooks et al., 2016). Within the auditory system specifically, spontaneous activity aids to also regulate hair cell maturation. However, how precisely spontaneous activity regulates hair cell maturation is not well understood. The true extent of the role of spontaneous activity in development, and even the generation of the activity itself, is still an area of dynamic research.
Understanding the full influence of spontaneous activity on inner hair cell maturation, especially during ribbon synapse development can provide insight into the development of the complex hair cell machinery. Additionally, it would be noteworthy to study inner hair cell development ex vivo in a context isolated from the central nervous system, as this could aid future investigations in drug development and the generation of novel targeted therapeutic strategies to combat hearing loss. Therefore, the aim of this project is to study how spontaneous activity (or lack thereof) in immature inner hair cells contributes to development and biophysical maturation of inner hair cells ex vivo by utilising optogenetic techniques and super resolution imaging.
