Dopamine transporter immunoreactivity in monkey cerebral cortex: Regional,laminar, and ultrastructural localization

Dopamine IDA) influences a number of cognitive and motor functions that are mediated by the primate cerebral cortex, and the DA membrane transporter ( DAT) is known to be a critical regulator of DA neurotransmission in subcort ical structures in rodents. To gain insight into the possible functional ro le of cortical DAT, we compared the regional, laminar, and ultrastructural distribution of DAT immunoreactivity to that of tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis, in the cerebral cortex of macaque monkeys. DAT-immunoreactive (DAT-IR) axons were present throughout the cor tical mantle, with substantial differences in density and laminar distribut ion across cytoarchitectonic areas. In particular, high densities of DAT-IR axons were present in certain regions (e.g., posterior parietal cortex, de ntate gyrus) not previously thought to receive a substantial DA input. The laminar distribution of DAT-IR axons ranged from a restricted localization of labeled axons to layer 1 in lightly innervated regions to the presence o f axons in all six cortical layers, with a particularly dense plexus in dee p layer 3, in highly innervated regions. These regional and laminar pattern s paralleled those of TH-IR axons, but several differences in fiber morphol ogy and ultrastructural localization of DAT were observed. For example, in contrast to TH, DAT immunoreactivity in the cortex was localized predominan tly to small-diameter profiles, whereas, in the dorsolateral caudate nucleu s, DAT and TH immunoreactivities were present in both large-diameter and sm all-diameter profiles, which may represent varicose and intervaricose axon segments, respectively. Overall, the distribution of DAT-IR axons confirms and extends the results of previous reports, using other markers of DA axon s, that the DA innervation of the primate cerebral cortex is global but spe cialized on both a regional basis and a laminar basis. In particular, these observations reveal an anatomical substrate for a direct and potent influe nce of DA over neuronal activity in posterior parietal cortex and in certai n regions of the temporal lobe. However, due to its predominant distributio n to small-diameter profiles, immunoreactivity for DAT may not be an approp riate ultrastructural marker for larger DA varicosities in the primate cort ex. Moreover, this distribution of DAT suggests that cortical DA fibers may permit greater neurotransmitter diffusion than subcortical DA axons. (C) 2 001 Wiley-Liss, Inc.