Dopamine has been implicated in the pathophysiology of schizophrenia, and the entorhinal cortex (ERC) is thought to be a site of structural pathology in this disorder. However, relatively little is known about the dopaminergic (DA) innervation of ERC in the primate brain. In this study, immunohistochemical methods and antibodies directed against tyrosine hydroxylase (TH) and dopamine were used to determine the organization of DA axons in the ERC of macaque monkeys. The anti-TH antibody used in this study appeared predominantly to identify DA axons, as demonstrated by its failure to label fibers that were immunoreactive with an antibody against dopamine-β-hydroxylase in double-labeling experiments. In addition, the regional and laminar distributions of TH-immunoreactive fibers were strikingly similar to those labeled with the anti-dopamine antibody.
With both antibodies, cytoarchitectonically identified subdivisions of monkey ERC (Amaral et al., 1987) differed in both the density and laminar distribution of labeled fibers. Immunoreactive processes exhibited a substantial rostral-to-caudal gradient of decreasing density across subdivisions of ERC, and the density of labeled fibers also decreased from medial to lateral in the rostral but not in the caudal subdivisions of ERC. The laminar distribution of labeled fibers differed both between and within subdivisions. For example, in the olfactory and rostral subdivisions of ERC, the superficial layers contained a very high density of immunoreactive processes, whereas in the intermediate region, three bands of labeled fibers were seen in layers I, III-IV, and VI. In addition, radial columns of fibers interdigi-tated with areas of decreased density were present between layers I and III. Although the overall density of labeled fibers was greater in lateral than in the caudal subdivisions of ERC, these regions had similar laminar distribution patterns. In these areas of monkey ERC, labeled processes were highest in density in deep layer I, and homogeneously distributed in the other cortical layers.
These findings demonstrate that the DA innervation of monkey ERC is complex, and follows laminar- and subdivision-specific patterns. These patterns of distribution suggest the possible interactions that DA axons may have with other elements of ERC circuitry, and may provide insight into the possible functional roles of dopamine in ERC in both normal and disease states.