Quantitative localization of NMDAR1 receptor subunit immunoreactivity in inferotemporal and prefrontal association cortices of monkey and human

The cellular and synaptic localization of immunoreactivity for the N-methyl-D-aspartate (NMDA) receptor subunit, NMDAR1, was investigated in inferotemporal and prefrontal association neocortices of monkeys and humans. In all monkey association areas examined, the laminar distribution patterns of NMDAR1 immunoreactivity were similar, and characterized by predominant pyramidal-like neuronal labeling in layers II, III, V and VI and a dense neuropil labeling consisting of intensely stained puncta and fine-caliber processes present throughout layers I-III, and V-VI. Layer IV, in contrast, contained only very lightly immunostained neurons which mostly lacked extensive dendritic staining. The laminar distribution of NMDAR1 immunolabeling in human association cortex was similar to that observed in monkeys. Electron microscopy of monkey areas 46 and TE1 confirmed that intensely immunoreactive asymmetrical postsynaptic densities were present throughout all cell-dense layers of prefrontal and inferotemporal association cortex. Quantitative analyses of the laminar proportions of immunoreactive synapses demonstrated that in both areas examined, the percentages of immunolabeled synapses were mostly similar across superficial layers, layer IV and infragranular layers. Finally, quantitative double-labeling immunofluorescence for non-NMDA receptor subunits or calcium-binding proteins demonstrated that virtually all GluR2/3 or GluR5/6/7-immunoreactive neurons were also labeled for NMDAR1, while regionally-specific subsets of parvalbumin-, calbindin- and calretinin-immunoreactive neurons were co-labeled. These data indicate that in primate association cortex, NMDA receptors are heterogeneously distributed to subsets of functionally distinct types of neurons and subsets of excitatory synapses, suggesting a critical and highly specific role in mediating the activity of excitatory connectivity which converges on cortical association areas.