Abnormal levels of acoustic activity can result in hearing problems such as tinnitus and language processing disorders, but the underlying cellular and synaptic changes triggered by abnormal activity are not well understood. To address this issue, we studied the time course of activity-dependent changes that occur at auditory nerve synapses in mice of both sexes after noise exposure and conductive hearing loss. We found that EPSC amplitude and synaptic depression decreased within 2 d of noise exposure through a decrease in the probability of vesicle release ( P r). This was followed by a gradual increase in EPSC amplitude through a larger pool of releasable vesicles ( N ). Occlusion of the ear canal led to a rapid decrease in EPSC amplitude through a decrease in N , which was followed by an increase in EPSC amplitude and synaptic depression through an increase in P r. After returning to normal sound levels, synaptic depression recovered to control levels within 1–2 d. However, repeated exposure to noise fo...