QUANTITATIVE LOCALIZATION OF NMDAR1 RECEPTOR SUBUNIT IMMUNOREACTIVITYIN INFEROTEMPORAL AND PREFRONTAL ASSOCIATION CORTICES OF MONKEY AND HUMAN

The cellular and synaptic localization of immunoreactivity for the N-m ethyl-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 distribu tion patterns of NMDAR1 immunoreactivity were similar, and characteriz ed 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, an d V-VI. Layer IV, in contrast, contained only very lightly immunostain ed neurons which mostly lacked extensive dendritic staining. The lamin ar distribution of NMDAR1 immunolabeling in human association cortex w as 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 o f prefrontal and inferotemporal association cortex. Quantitative analy ses of the laminar proportions of immunoreactive synapses demonstrated that in both areas examined, the percentages of immunolabeled synapse s were mostly similar across superficial layers, layer IV and infragra nular layers. Finally, quantitative double-labeling immunofluorescence for non-NMDA receptor subunits or calcium-binding proteins demonstrat ed that virtually all GluR2/3 or GluR5/6/7-immunoreactive neurons were also labeled for NMDAR1, while regionally-specific subsets of parvalb umin-, calbindin- and calretinin-immunoreactive neurons were co-labele d. These data indicate that in primate association cortex, NMDA recept ors are heterogeneously distributed to subsets of functionally distinc t types of neurons and subsets of excitatory synapses, suggesting a cr itical and highly specific role in mediating the activity of excitator y connectivity which converges on cortical association areas.