The monoaminergic innervation of cerebral cortex has long been implicated in its development. Methods now exist to examine catecholamine and serotonin inputs to identified neurons in the cerebral cortex. We have quantified such inputs on pyramidal and nonpyramidal cells in prefrontal cortex of rhesus monkeys ranging in age from 2 weeks to 10 years. Individual layer III neurons were filled with Lucifer yellow and double-immunostained with axons containing either tyrosine hydroxylase (TH) or 5-hydroxytryptamine (5-HT). The filled cells were reconstructed, and putative appositions between the axons and dendritic spines and shafts were quantified at high magnification using light microscopy. The density of catecholamine appositions on pyramidal neurons matures slowly, reaching only half the adult level by 6 months of age and thereafter rising gradually to adult levels by 2 years of age. By contrast, the density of serotonin appositions on pyramidal cells reaches the adult level before the second week after birth. The average adult pyramidal neuron in layer III of area 9m receives three times stronger input from catecholaminergic than from serotoninergic axons. The overall density of both inputs to interneurons does not appear to change during postnatal development. Selective changes in the TH innervation of pyramidal cells against a backdrop of constant TH innervation of interneurons suggest that the balance between excitation and inhibition may change developmentally in the prefrontal cortex. By contrast, 5-HT innervation of both types of neurons remains relatively constant over the age range studied.
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