Prenatal development of neurons in the human prefrontal cortex: I. A qualitative Golgi study

Golgi-Stensaas and rapid-Golgi staining techniques are used to study neuronal differentiation in the developing human prefrontal cortex in fetuses, premature infants, and full-term newborns from 10.5 to 40 weeks of gestation. Horizontal neurons (Cajal-Retzius neurons) above the cortical plate (in the marginal zone) and randomly oriented neurons below the cortical plate (in the primordial subplate) are more differentiated than the immature bipolar cortical plate neurons in the 10.5-week fetus. During 13.5-15 weeks of gestation the fetal subplate zone can be clearly distinguished-between the cortical plate and the intermediate zone. This subplate zone contains more mature neurons than the cortical plate, especially polymorphous neurons. The basic features of the apical and basal dendrites of pyramidal neurons develop between 17 and 25 weeks of gestation, before the thalamocortical fibres invade the cortical plate. Intensive differentiation of the subplate neurons occurs in this period, when various types of afferent fibres reside in the subplate zone. At least five neuronal types can be distinguished in the subplate, i.e., polymorphous, fusiform, multipolar, normal, and inverted pyramidal neurons. The ingrowth of afferent fibres into the cortical plate between 26 and 34 weeks of gestation coincides with intensive dendritic differentiation and the appearance of spines on dendrites of the prospective layer III and V pyramidal neurons as well as with the differentiation of the double bouquet interneurons in the prospective supragranular layers and layer IV. Multipolar nonpyramidal neurons with the dendritic features of basket neurons are observed between 32 and 34 weeks of gestation in future layer V. They are less differentiated than the double bouquet neurons. The neurons of the subplate zone continue their dendritic differentiation after 26/27 weeks of gestation and are still observed in the full-term newborn. The axonal pattern of the subplate neurons suggests a possible functional role for them as either interneurons or projection neurons.