Differential ontogenic development of three receptors comprising the NMDA receptor/channel complex in the rat...

The postnatal development of the three receptor binding sites that constitute the N-methyl-D-aspartate (NMDA) receptor channel/complex was examined in six hippocampal regions of rats using quantitative receptor autoradiography. NMDA-sensitive [3H]-glutamate binding, strychnine-insensitive [3H]glycine binding, and [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine [( 3H]TCP) binding were measured to examine the ontogeny of NMDA recognition sites, glycine modulatory sites, and PCP receptors, respectively. NMDA-sensitive [3H]glutamate binding transiently exceeded adult levels by 50 to 120% in all regions examined, with peak densities generally occurring between postnatal days (PND) 10 and 28. Stratum radiatum CA1 binding increased slowly from 49 to 61% of the adult value between PND 1 and 7, after which, binding rapidly rose to 151% of adult values at PND 14, remained elevated through PND 28, and then decreased to adult levels. The ontogenic profile of NMDA recognition site binding was similar in other hippocampal regions, although the initial age of maximal binding and the period of stabilization varied. The ontogenic profiles of glycine modulatory site binding and PCP receptor binding were very similar to each other. Development was delayed, however, with respect to NMDA recognition site binding. The rapid development of binding observed between PND 7 and 14 with NMDA receptors in stratum radiatum CA1 was contrasted by a much slower increase in glycine and PCP receptor binding. Furthermore, maximal glycine and PCP receptor binding densities were not reached until PND 28 and were lower than NMDA recognition site binding densities. The observed developmental patterns of binding to each of the receptor components of the NMDA receptor channel/complex are consistent with postnatal changes in cytoarchitecture, synaptogenesis, afferent lamination, and functional development of the hippocampus. However, the relative overexpression of NMDA recognition sites with respect to glycine and PCP receptors between PND 7 and 21 suggests that there is differential expression of these binding sites during development.