Possible mechanisms underlying presynaptic or postsynaptic auditory neuropathy. In the healthy cochlea (Normal) an auditory input transmitted from an outer hair cell (OHC) evokes a synchronized discharge of auditory nerve fibers. In presynaptic AN, both the reduction and the increased time of neurotransmitter release result in decreased postsynaptic activation (decreased input) and elicitation of EPSPs with abnormal morphology leading, in turn, to a reduction of occurrence of and increased time to spike initiation (desynchrony). This mechanism is likely to underlie AN in patients carrying OTOF mutations. In postsynaptic AN, there is a decrease in activated auditory fibers (decreased input), abnormalities in spike occurrence with slowing in conduction velocity, which results in loss of temporal precision and stimulus correlation of auditory nerve fiber discharge (desynchrony). Genes implicated in pre- and postsynaptic AN, respectively, are shown in the boxes.