The activity of neuronal circuits of the neocortex underlies our ability to perceive the world and interact with our environment. During development, these circuits emerge from dynamic interactions between cell-intrinsic, genetically determined programs and input/activity-dependent signals, which together shape these circuits into adulthood. Building on a large body of experimental work, several recent technological developments now allow us to interrogate these nature–nurture interactions with single gene/single input/single-cell resolution. Focusing on excitatory glutamatergic neurons, this review discusses the genetic and input-dependent mechanisms controlling how individual cortical neurons differentiate into specialized cells to assemble into stereotypical local circuits within global, large-scale networks.
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