Identifying roles for neurotransmission in circuit assembly: Insights gained from multiple model systems and experimental approaches

In the adult nervous system, chemical neurotransmission between neurons is essential for information processing. However, neurotransmission is also important for patterning circuits during development, but its precise roles have yet to be identified, and some remain highly debated. Here, we highlight viewpoints that have come to be widely accepted or still challenged. We discuss how distinct techniques and model systems employed to probe the developmental role of neurotransmission may reconcile disparate ideas. We underscore how the effects of perturbing neurotransmission during development vary with model systems, the stage of development when transmission is altered, the nature of the perturbation, and how connectivity is assessed. Based on findings in circuits with connectivity arranged in layers, we raise the possibility that there exist constraints in neuronal network design that limit the role of neurotransmission. We propose that activity-dependent mechanisms are effective in refining connectivity patterns only when inputs from different cells are close enough, spatially, to influence each other's outcome.