Mechanisms driving the functional maturation of the developing mammalian auditory pathway.

The accurate representation of sound in the central auditory pathway of mammals depends on the cochlea, the peripheral sensory organ, which is optimised to detect acoustic signals with unparalleled temporal precision. Beyond its role in converting acoustic stimuli into electrical signals, the cochlea also plays a key role in shaping the maturation of the auditory pathway during pre-hearing stages. This process is essential for creating the tonotopic maps used to identify a broad range of sound frequencies. To achieve this extraordinary task, the sensory hair cells and supporting cells of the pre-hearing cochlear sensory epithelium generate spontaneous, sensory-independent Ca²⁺ signals that propagate along the ascending auditory pathway. Here we review the current understanding of how the different Ca²⁺ signals are generated within the developing cochlea, how they interact to regulate the activation of the auditory afferent fibres, and how they ultimately contribute to the establishment of a mature auditory system pathway. Remarkably, a partial regression to an immature developmental stage occurs in the ageing cochlea, correlated with age-related hearing loss. Increasing our understanding of how the cochlear epithelium changes during all stage of life will inform future therapies for preventing and to reverse hearing loss.