The role of spontaneous neurotransmission in synapse and circuit development

In the past, the spontaneous release of neurotransmitter from presynaptic terminals has been thought of as a side effect of evoked release, with little functional significance. As our understanding of the process of spontaneous release has increased over time, this notion has gradually changed. In this review, we focus on the importance of this form of release during neuronal development, a time of extreme levels of plasticity that includes the growth of dendrites and axons as well as the formation of new synaptic contacts. This period also encompasses high levels of neurotransmitter release from growing axons, and recent studies have found that spontaneous transmitter release plays an important role in shaping neuronal morphology as well as modulating the properties of newly forming synaptic contacts in the brain. Here, we bring together the latest findings across different species to argue that the spontaneous release of neurotransmitter is an important player in the wiring of the brain during development.