Differential Postnatal Development of Catecholamine and Serotonin Inputs to Identified Neurons in Prefrontal Cortex of Rhesus Monkey

Abstract

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 doubleimmunostained 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.Key words: tyrosine hydroxylase; dopamine; serotonin; 5-hydroxytryptamine; pyramidal neuron; interneuron; rhesus monkey; nonhuman primate; prefrontal cortex Monoaminergic systems of the brain modulate excitatory transmission in cortical circuits that are critical for normal adult function of prefrontal cortex (Williams and Goldman-Rakic, 1995;Vollenweider et al., 1998). The same neurotransmitters have been implicated directly and indirectly in several aspects of neurodevelopment (Mattson, 1988;Levitt et al., 1997), in the pathophysiology of schizophrenia (Lieberman, 1999), and in the psychotomimetic effects of certain hallucinogens (Breier, 1995;Farber et al., 1999;Gouzoulis-Mayfrank et al., 1999). There are timing similarities among the attainment of peak working memory performance (Diamond and Goldman-Rakic, 1989), the typical age of onset of schizophrenia (Lieberman, 1999), and the age at which certain drugs begin to trigger psychosis (Farber et al., 1999). These developmental parallels suggest that a detailed understanding of the postnatal changes in monoaminergic input to cortical neurons may shed light on the changes in circuitry needed for mature working memory performance, as well as on how this circuitry may become disrupted in psychosis.Monoamines have been extensively studied during embryonic development (Lauder and Bloom, 1974;Coyle and Molliver, 1977;Buznikov, 1984;Mattson, 1988;Verney et al., 1993;Levitt, 1...

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