Development of the dopaminergic innervation of the rat cerebral cortex. A light microscopic immunocytochemical study using anti-tyrosine hydroxylase antibodies.

A precise topographical analysis of the distribution of tyrosine hydroxylase-like immunoreactive processes was performed in the frontal, cingular and parietal cortex of the rat during late embryonic and early postnatal life. Until birth, labeled processes were only observed in the restricted cortical areas known to receive a dopaminergic innervation in the adult brain. Their distribution differed markedly from that of noradrenergic fibers as identified by their dopamine-beta-hydroxylase-like immunoreactivity. Thus we considered TH-like immunoreactivity to be a selective marker of the cortical dopaminergic innervation during late fetal life, at least with the antibody we used. With this marker, dopaminergic fibers were first detected in the anterior frontal cortex at day 16 of embryonic life (E16). They developed as two bundles passing medially and laterally to the ventricular layer without penetrating it. From E20 on, the terminal fields extended to the cingular and rhinal cortex, still being restricted to the intermediate zone. No fibers were visible in the lateral and dorsal frontal cortex at this time, nor in the cortical plate and molecular layer in any cortical area. At E21, rare labeled fibers were seen in the molecular layer of the medial frontal and cingular cortex. After birth, the terminal fields of the TH-containing fibers extended further caudally in the cingular cortex and also superficially in the cortical plate. Moreover, labeled axons now also appeared in the lateral frontal and parietal cortex where their density gradually increased. At P14, two different patterns of distribution were observed: a high density of TH-positive fibers in the cortical areas known to receive a dopaminergic innervation; a low density of fibers in the other cortical areas which represented noradrenergic fibers. Indeed these TH-containing presumed noradrenergic fibers were absent at P14 following a bilateral destruction of the locus coeruleus in 4-day-old pups.