A quantitative electron-microscopic (EM) analysis of the development of synaptic density (number of synapses/100 μm neuropil) has been done in primary visual cortex (striate, area 17) of the Old World monkey Macaca nemesthna. A comparative EM morphological study of developing synaptic contacts also was done in the same tissue. We find that a few immature synaptic contacts are present at fetal (F) 75 days either in the marginal zone, which becomes layer 1, or in the deepest portion of the cortical plate, the future layer 6. At F90–140 days synaptic contacts are found throughout the cortical plate, but their density remains higher in lower cortical layers. By F140 days synaptic density averaged for all layers (10.9) is three times higher than at F90 days. Just before and after birth, synaptic density rises very rapidly to peak at postnatal (P)12 weeks (63) and then declines slowly to reach adult values (37.7) between 2–6 years. This pattern was further tested by comparing synaptic density in layer 2 which contains the last cells generated in the striate cortex to that in layer 6 which contains the first cells generated in the striate cortex. Layer 6 contained the first synapses, and had a higher density up to F140 days (an “inside-to-outside” distribution). Synaptic density was equal in the two layers at F152 days and P2 days, but by P12 weeks synaptic density in layer 2 was 27% higher than that in layer 6 (an “outside-to-inside” distribution). After P12 weeks, the synaptic density declined 51% in layer 2 and 21% in layer 6 so that both layers achieved similar densities by P6 years.

A light and EM comparison of neuropil and synaptic contact morphology finds that, at each age up to birth, synapses in layer 2 are generally less mature than those in layer 6, but these differences disappear shortly after birth. Between P6–24 weeks, synaptic contacts throughout the cortex acquire a mature morphology that clearly differentiates between asymmetric and symmetric types, although asymmetric contacts continue to acquire more postsynaptic density until adulthood.

This complex developmental pattern suggests a sequence for synaptic developments which is more related to neuron birthdate than to the arrival of extrinsic pathways or developmental events occurring in specific laminae.