Synaptic development in the human fetus: a morphometric analysis of normal and Down's syndrome neocortex

Postmortem tissue was obtained from six normal and four Down's syndrome brains ranging in age from 12 to 40 weeks postconception. Tissue was processed for electron microscopy using routine osmium and EPTA staining procedures, and to examine synaptic development, photomicrographs were systematically taken throughout the molecular layer of the sensorimotor neocortex. The number of EPTA-stained synapses were consistently greater than the number of osmium-stained synaptic contacts. A progressive increase in synaptic density throughout the range of ages examined was observed for both normal and Down's syndrome tissue. There was also an increase with developmental age in apparent measures of synaptic maturity, e.g., an increased ratio of mature to primitive contacts and asymmetrical to symmetrical contacts. In normal tissue, pre- and postsynaptic membrane lengths were observed to increase with the ages studied, whereas synaptic membrane widths appeared to attain mature values by 29 weeks postconception. Cleft width remained fairly constant to 28 weeks postconception. Although direct statistical comparisons could not be made, in Down's tissue synaptic parameter development was generally less consistent and the parameters appeared to be reduced during the later stages of development studied.