Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life.

The density and proportion of synaptic contacts in the primate motor cortex (Brodmann area 4) were determined in 21 rhesus monkeys ranging in age from embryonic day 41 (E41) to 20 years. Two to 4 vertical electron microscopic probes, each consisting of 150-250 overlapping micrographs traversing the thickness of the cortex, were prepared for each specimen. Synapses were categorized according to their morphology (symmetrical or asymmetrical), cellular location (on spines, shafts or soma), number, and ratio of laminar distribution. The density of synapses was expressed per unit area and volume of neuropil (excluding neuronal and glia cell bodies, myelin sheath, blood vessels and extracellular space). The first synapse in the area of the emerging motor cortex were observed at E53 in the marginal zone (prospective layer I) and in the transient subplate zone situated beneath the developing cortical plate. Around midgestation (E89) synapses were observed over the entire width of the cortical plate, and their density was about 5/100 microns 3 of neuropil. During the last two months of gestation synaptic density increased 8-fold across all layers to reach about 40/100 microns 3 at the time of birth (E165). Synaptic production continued postnatally and by the end of the second postnatal month attained a level of 60/100 microns 3 neuropil which is two times higher than in the adults. This level decreased at a slow rate until sexual maturity (3 years of age) and then more rapidly to the adult level which is characterized by relative stability of about 30/100 microns 3. The decline in synaptic density after the peak in infancy occurs predominantly at the expense of asymmetric synapses situated on dendritic spines; the population of symmetric synapses on dendritic shafts remains relatively constant. The development of synaptic connections in the motor cortex of non-human primates involves initial overproduction followed by selective elimination and structural alterations.