IMMUNOCYTOCHEMICAL EVIDENCE OF WELL-DEVELOPED DOPAMINERGIC AND NORADRENERGIC INNERVATIONS IN THE FRONTAL CEREBRAL-CORTEX OF HUMAN FETUSES AT MIDGESTATION

The catecholaminergic (CA) innervation of the frontal lobe was visuali zed in 20- to 24-week-old human fetuses with immunocytochemical techni ques, by use of antibodies raised against three synthetic enzymes of t he CA pathway, tyrosine-hydroxylase (TH), dopamine-beta-hydroxylase (D BH), and phenylethanolamine-N-methyltransferase (PNMT). DBH-like immun oreactivity (IR) was probably labeling the noradrenergic (NA) fibers a nd terminals in the cerebral cortex since no PNMT-IR fibers were detec ted. In double-labeling TH-DBH experiments, 92-95% of the DBH-IR affer ents were not labeled with TH antibodies, indicating that TH-like immu noreactivity (TH-IR) was found primarily in dopaminergic (DA) fibers. Although cortical layering had not yet occurred at this stage, the wid espread CA innervation observed in the different areas and layers of t he fetal frontal cortex was comparable to that previously described in the adult (Gaspar, Berger, Febvret, Vigny, and Henry: J. Comp. Neurol . 279:249-271, '89). At midgestation, the distribution of CA innervati on was region and laminar specific: 1) The densest dopaminergic innerv ation in the cerebral cortex was located caudal to the genu of the cor pus callosum: TH-IR fibers were abundant throughout all layers, from t he medial telencephalon (future cingulate) to the dorsal areas (presum ed motor cortices) and the lateral insular areas; 2) TH-IR fibers were less dense in the rostral prefrontal cortical anlage; 3) DBH-IR norad renergic afferents were less numerous than the dopaminergic ones in al l the cortical areas studied; 4) in all areas, the highest amount of T H and DBH-IR terminals was found in the upper subplate and in the lowe r part of the cortical plate, followed by the molecular layer and the intermediate zone. The deep subplate exhibited a lower number of posit ive fibers but contained TH-IR cell bodies. The presence of dense CA i nnervation in the immature cortical anlage of the human frontal lobe d oes not exclude a reorganization of DA and NA innervations within the different cortical layers and areas during the protracted pre- and pos tnatal period of development. (c) 1993 Wiley-Liss, Inc.