Subcellular and subsynaptic distribution of the NR1 subunit of the NMDA receptor in the neostriatum and globus pallidus of the rat: co-localization at synapses with the GluR2/3 subunit of the AMPA receptor

Glutamatergic neurotransmission in the neostriatum and the globus pallidus is mediated through NMDA-type as well as other glutamate receptors and is c ritical in the expression of basal ganglia function. In order to characteri ze the cellular, subcellular and subsynaptic localization of NMDA receptors in the neostriatum and globus pallidus, multiple immunocytochemical techni ques were applied using antibodies that recognize the NR1 subunit of the NM DA receptor. In order to determine the spatial relationship between NMDA re ceptors and AMPA receptors, double labelling was performed with the NR1 ant ibodies and an antibody that recognizes the GluR2 and 3 subunits of the AMP A receptor. In the neostriatum all neurons with characteristics of spiny projection neu rons, some interneurons and many dendrites and spines were immunoreactive f or NR1. In the globus pallidus most perikarya and many dendritic processes were immunopositive. Immunogold methods revealed that most NR1 labelling is associated with asymmetrical synapses and, like the labelling for GluR2/3, is evenly spread across the synapse. Double immunolabelling revealed that in neostriatum, over 80% of NR1-positive axospinous synapses are also posit ive for GluR2/3. In the globus pallidus most NR1-positive synapses are posi tive for GluR2/3. In both regions many synapses labelled only for GluR2/3 w ere also detected. These results, together with previous data, suggest that NMDA and AMPA rece ptor subunits are expressed by the same neurons in the neostriatum and glob us pallidus and that NMDA and AMPA receptors are, at least in part, colocal ized at individual asymmetrical synapses. The synaptic responses to glutama te in these regions are thus likely be mediated by both AMPA and NMDA recep tors at the level of individual synapses.