Dopamine Axons in Primate Prefrontal Cortex: Specificity of Distribution, Synaptic Targets, and Development

Abstract

The substantial specificity in innervation patterns, synaptic targets, and postnatal development exhibited by dopamine (DA) axons may provide insight into the role of these afferents in the functional architecture of the prefrontal cortex (PFC), in both normal and disease states. In addition, abnormalities in DA neurotransmission have been implicated in the pathophysiology of certain disorders, such as schizophrenia, that are associated with disturbances in the cognitive functions subserved by the PFC. The researchers have examined the regional and laminar innervation patterns of DA axons in monkey PFC, their synaptic targets, and their maturational changes during postnatal development. Within the monkey cerebral cortex, the distribution of DA transporter-immunoreactive (DAT-IR) axons differed substantially across cytoarchitectonic regions. In most areas, DAT-labeled axons in the PFC have been distributed in a bilaminar fashion, with the density of labeled axons greatest in the superficial layers (I-IIIa), intermediate in the deep layers (Vb-VI), and very low in the middle layers (IIIb-Va). This apparent specificity of the synaptic targets of DA axons has been further demonstrated by the fact that THpositive terminals do not form synapses with CR-containing dendrites in the superficial cortical layers of monkey PFC, although synaptic contacts between tyrosine hydroxylase-immunoreactive (TH-IR) terminals and GABA-labeled dendrites are clearly present in these layers The synaptic regulation of parvalbumin (PARV) -containing local circuit neurons by DA is particularly interesting, given the potent inhibitory control that these neurons may exert on pyramidal cells. These findings may reflect differences in the subcellular localization of TH and DAT and the different role that these two proteins play in the regulation of DA neurotransmission.