Expression of the N-methyl-D-aspartate receptor subunit R1 in the developing human hippocampus

It has been suggested that the N-methyl-D-aspartate (NMDA) receptor family plays a key role in synaptic plasticity and synaptogenesis that is essential for memory, learning, differentiation, and development. Although gene expression of these receptors has been analyzed in the experimental animal brain and in some diseases of the adult or elderly human brain, it has not been studied in the developing human brain. Using in situ hybridization, we investigated the expression of the NMDAR1 gene in the hippocampi of 16 human neonates who were between 22 and 40 weeks of gestation and had no evidence of critical episodes of brain insult at autopsy. Signals for NMDAR1 were detected ubiquitously at all developmental stages. Dense hybridization signals were uniformly detected in the granular cells of the dentate gyrus in all specimens. Stronger signals were observed in the larger-type pyramidal cells in the CA2 and CA3 regions compared with the pattern seen in the CA1 region in the smaller-type pyramidal cells. These results suggest that the NMDAR1 gene is expressed at 22 weeks and possibly occurs earlier in neuronal cell bodies of the dentate gyrus and all CA fields of Ammon's horn and that the NMDAR plays an important role in constructing neuronal networks in developing human brains.