Activity-dependent changes in the synaptic connections of the brain are thought to be important for learning and memory. Imaging techniques have enabled the examination of structural rearrangements during activity-dependent processes at the synapse. While many studies have examined structural changes of dendritic spines, little is known about structural plasticity of presynaptic boutons. We therefore examined how axonal boutons are affected during long-term depression (LTD). We used time lapse two-photon laser scanning microscopy and extracellular field recordings to monitor simultaneously synaptic morphology and activity for up to five hours in mouse organotypic hippocampal slice cultures. LTD induction dramatically increased the turnover of presynaptic boutons, while decreasing the number of putative synaptic contacts between Schaffer collateral boutons and spines of CA1 pyramidal cells. Our data indicate a substantial presynaptic contribution to activity-dependent morphological plasticity and provide opportunities for studying the molecular mechanisms of the structural remodeling of synaptic circuits.