Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life

Before hearing onset, inner hair cell (IHC) maturation proceeds under the influence of spontaneous Ca(2+) action potentials (APs). The temporal signature of the IHC Ca(2+) AP is modified through an efferent cholinergic feedback from the medial olivocochlear bundle (MOC) and drives the IHC pre- and post-synapse phenotype towards low spontaneous (spike) rate (SR), high-threshold characteristics. With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics. Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step. In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system. In particular, we examine several IHC synaptopathies in the context of various hearing disorders and exemplified shortfalls before and after hearing onset.