Beyond the connectome: How neuromodulators shape neural circuits

Powerful ultrastructural tools are providing new insights into neuronal circuits, revealing a wealth of anatomically‐defined synaptic connections. These wiring diagrams are incomplete, however, because functional connectivity is actively shaped by neuromodulators that modify neuronal dynamics, excitability, and synaptic function. Studies of defined neural circuits in crustaceans, C. elegans, Drosophila, and the vertebrate retina have revealed the ability of modulators and sensory context to reconfigure information processing by changing the composition and activity of functional circuits. Each ultrastructural connectivity map encodes multiple circuits, some of which are active and some of which are latent at any given time. The connectome anatomically describes the entire synaptic connections in a given brain. However, there seem to be more connections than absolutely necessary, and neuromodulators specify which of these connections are active at any given time.