Synapses change their strength in response to specific activity patterns. This functional plasticity is assumed to be the brain’s primary mechanism for information storage. We combine optogenetic and chemogenetic control of synapses in rat hippocampal slice cultures with calcium and glutamate imaging of their spines and boutons. This approach enables us to perform all-optical quantal analysis of synaptic transmission, to induce long-term potentiation (LTP), long-term depression (LTD), or both forms of plasticity in sequence, to chronically manipulate activity and to follow the fate of individual synapses for 7 days. We ask how plasticity and activity are integrated at Schaffer collateral synapses over time. Our findings suggest that activity-dependent changes in the transmission strength of individual synapses are transient, but have long-lasting consequences for synaptic lifetime.