Density and distribution of excitatory amino acid receptors in the developing human fetal brain: a quantitative...

The binding of [alpha-3H]amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to quisqualate receptors, [3H]kainate (KA) to KA receptors, and L-[3H]glutamate to N-methyl-D-aspartate (NMDA) receptors was determined by quantitative autoradiography in brains obtained from twelve aborted human fetuses ranging from 16.5 to 26 weeks of gestational age. Among the three receptor subtypes, specific binding to AMPA was the highest, followed by NMDA and KA, respectively, in all age groups. Receptor binding was already apparent by 16.5 weeks in the hippocampus, thalamus, and subthalamic nucleus, rose sharply by 20-21.5 weeks, and subsequently declined to their lowest levels by 24-26 weeks. Anatomically distinct binding patterns for each of the three major excitatory amino acid (EAA) receptor subtypes were well established by 20-21.5 weeks. Within the hippocampus, AMPA was localized primarily in the stratum pyramidale, NMDA in the stratum radiatum, and KA in the molecular layer of the dentate gyrus and in the stratum lucidum of the CA3 region. The cerebral cortex showed dense labeling of AMPA in the outer layers, whereas KA binding was more prominent within the inner layers. The putamen and globus pallidus also showed relatively dense receptor binding in all age groups. The sharp rise in receptor density at 20-21.5 weeks of age suggests involvement of EAA pathways in developmental plasticity, including reorganization of neuronal processes or synapses, during this period of development. Developmental changes in the density and distribution of EAA receptors, as shown in this study, may also provide insight into shifts in the localization of age-dependent selective vulnerability within the developing human fetal brain.