The role of neuronal activity and transmitter release on synapse formation

•Synaptic activity drives the formation of specific synapses in the retina.•Neurotransmitter induces the formation of spines in developing cortical neurons.•Axons are capable of releasing neurotransmitter before synaptic contacts.•We speculate on the role of early, non-synaptic release in synaptogenesis.

The long history of probing the role of neuronal activity in the development of nervous system circuitry has recently taken an interesting turn. Although undoubtedly activity plays a critical part in the maintenance and refinement of synaptic connections, often via competitive mechanisms, evidence is building that it also drives the process of synapse formation itself. Perhaps predictably, this turns out not to be a uniform process. It seems that different circuits, indeed specific synaptic connections, are differentially sensitive to the effects of activity. We examine possible ways in which neurotransmitter may drive synapse formation, and speculate on how the environment of the developing brain may allow a different spatiotemporal range for neuronal activity to operate in the generation of connectivity.