Abstract A fundamental unanswered question in developmental neuroscience is how precise connections are made between nerves and their appropriate target muscles in embryos. This study uses a defined model system consisiting of nerve cell and muscle cell cultures from embryos of the frog Xenopus to address this issue. The studies are based on observations that repetitive electrical stimulation of a particular nerve cell induced a persistent depression in the activity of a another (heterosynaptic) nerve cell. This activity-dependent long-term modulation of the connection could be an important mechanism in establishing the functional nerve-muscle connections of the animal. Structural and physiological changes in the neuromuscular junctions are analysed using a variety of techniques, including the use of vital fluoresent dyes that can be injected into specific nerve cell and thus label them for subsequent identification.