The formation of synapses is among the most important steps in neurona
l differentiation and the establishment of neuronal circuits. To estab
lish baseline data about the time of onset, density and the course of
synaptic formation in different regions of the human cerebral cortex b
efore birth, synaptogenesis in layer I was examined by electron micros
copy in fetuses ranging in age from 6 to 24 gestational weeks. Synapse
s were first observed in the primordial plexiform layer (marginal zone
) in both the lateral and medial cerebral walls between the 6th and 7t
h gestational week, before the formation of the cortical plate. The de
nsity of synapses increased rapidly after the formation of the cortica
l plate, increasing by 37% between 12 and 14 weeks. Synaptogenesis pro
ceeded at the same rate in the lateral and occipital cortex during thi
s period. Further, with one exception, the insular region, synaptic de
nsity was comparable in prospective areas of prefrontal, motor, visual
, temporal and cingulate cortex in a group of fetuses at midgestation
(20 weeks). The results are consistent with a synchronous course of sy
naptogenesis of the neocortex.