Abstracts

Rationale: Synaptogenesis is an important developmental process in cerebral ontogeny. Until now, there has been no means of visualizing or measuring synaptogenesis except by electron microscopy. EEG maturation in preterm and term infants reflects synaptogenesis, but only in large fields of the developing cortex. Neuroimaging still cannot demonstrate synapses. Our purpose was to study the temporal and spatial sequence of synaptogenesis in human fetal brain using immunoreactivity for synaptophysin, a protein of the synaptic vesicle wall. Abnormal synaptogenesis may be a basis of some infantile epilepsies.Methods: We studied 158 normal human fetal and neonatal brains postmortem over a 28-month period, using synaptophysin and also correlative neuronal markers of maturation, with controls of older children. Gestational ages ranged from 6 to 41 weeks. The present study focused on the neocortex and hippocampus. Macerated brains of 12 stillborns were studied separately to determine autolytic degradation of synaptophysin.Results: Changes with advancing gestational age in synaptic reactivity were very evident(Figs. 1,2). The molecular zone of the dentate gyrus develops synaptic reactivity at 12wk, whereas the CA2 sector of Ammon’s horn reacts at 14wk, followed by CA3, then CA4 and finally CA1 at near-term. Neocortex exhibits earliest reactivity at 12wk, above and beneath, but not within, the cortical plate. Thalamocortical axons are weakly reactive at 12-13wk and strong at 24-28wk. Synapses surround neurons in deep layers at 30wk, followed by middle layers and lastly layer 2 at near-term. Primary motor, sensory and visual neocortex matured sooner than associative cortex. Synaptophysin resisted postmortem autolysis. Conclusions: The pattern of synaptic development is predictable and can correlate with EEG and clinical neurological maturation in preterm and term infants. Normal data provide a basis for understanding abnormal or delayed synaptogenesis in malformations, hypoxic/ischaemic and metabolic encephalopathies, and may help explain some infantile epilepsies.