Protein synthesis seems to be essential for consolidating changes in synapses associated with various forms of learning and memory (synaptic plasticity). However, at present, the relationships between gene expression, protein synthesis, synaptic maintenance and synaptic plasticity are far from clear. Dissecting these relationships, we believe, demands a novel systems biological approach capable of resolving the repertoire of newly synthesized proteins and their actual sites of synthesis (cell body, dendrite, or spine). Towards this goal, we have assembled a group of experts on the regulation of mRNA translation (Proud), molecular mechanisms underlying synaptic plasticity related to learning and memory (Rosenblum), synaptic plasticity related to long-term potentiation (LTP) and growth factor dependent synaptic plasticity (Bramham), and systems biology of the synapse proteome (Armstrong). We propose a collaborative programme that will examine how synapses modify and maintain their characteristics for long durations, with an emphasis on the roles of protein synthesis in these processes. The experimental strategy is designed to elucidate how minute, dynamic and remote synapses are maintained and modified in response to neural activity patterns. This information may ultimately help to explain how the brain, which is composed of labile, short-lived components, can both retain memories and, at the same time, form new ones. This information is crucial for understanding the molecular events that that lead to human neurological disease when such processes are defective.