Long‐term modification of synaptic strength is thought to be the basic mechanism underlying the activity‐dependent refinement of neural circuits and the formation of memories engrammed on them. Studies ranging from cell culture preparations to humans subjects indicate that the decision of whether a synapse will undergo strengthening or weakening critically depends on the temporal order of presynaptic and postsynaptic activity. At many synapses, potentiation will be induced only when the presynaptic neuron fires an action potential within milliseconds before the postsynaptic (...) neuron fires, whereas weakening will occur when it is the postsynaptic neuron that fires first. Such processes might be important for the remodeling of neural circuits by activity during development and for network functions such as sequence learning and prediction. Ultimately, this synaptic property might also be fundamental for the cognitive process by which we structure our experience through cause and effect relations. BioEssays 24:212–222, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10060. (shrink)