Noradrenergic innervation of monkey prefrontal cortex: a dopamine-beta-hydroxylase immunohistochemical study

Norepinephrine has been implicated in the regulation of a number of cortical functions, yet relatively little is known about the anatomical organization of noradrenergic axons in the expanded and highly differentiated prefrontal cortex of primates. In this study, the distribution of fibers containing dopamine-beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was characterized immunohistochemically in the prefrontal cortical regions of Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density of DBH-labeled fibers were detected both across and within many prefrontal cytoarchitectonic regions. In cynomolgus monkeys, area 8B had the greatest density of DBH-immunoreactive fibers; within this region, the medial surface had a greater density of labeled processes than the dorsal surface. Areas 9 and 24 also had a high density of DBH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and portions of areas 10 and 46 had the lowest density of immunoreactive fibers. Regional differences in the density of DBH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. Despite the regional variations in the density of DBH-immunoreactive fibers, the laminar distribution of these fibers was very similar across cytoarchitectonic areas of cynomolgus prefrontal cortex. Layer I contained a low density of labeled fibers which were primarily tangential in orientation. The predominantly radially oriented fibers in layers II-IV were slightly higher in density. The density of both radially and tangentially oriented immunoreactive fibers increased substantially in layer V. Fiber density decreased in layer VI; a band of tangentially oriented fibers was present in the deep portion of this layer. With a few exceptions, the laminar distribution of DBH-immunoreactive fibers in the prefrontal regions of squirrel monkey cortex was similar to that of cynomolgus monkey. Since other data suggest that anti-DBH selectively labels noradrenergic axons in monkey neocortex, the distinctive innervation patterns exhibited by DBH-immunoreactive fibers reveal the regions and layers that may be the principal sites of action of norepinephrine in exerting its effects on prefrontal cortical function.