N-methyl-D-aspartate receptor 1 in the caudate-putamen nucleus: ultrastructural localization and co-expression with...

Entry of calcium through N-methyl-D-aspartate-type glutamate receptors in the caudate-putamen nucleus is essential for normal motor activity, but can produce cytotoxicity with continued stimulation and subsequent release of intracellular calcium. To determine potential functional sites for N-methyl-D-aspartate receptor activation in this region, we examined the ultrastructural localization of the R1 subunit of the N-methyl-D-aspartate receptor (NMDAR1) in rat brain. In addition, we comparatively examined the localization of NMDAR1 and sorcin, a 22,000 mol. wt calcium binding protein present in certain striatal neurons and involved in calcium-induced calcium release. NMDAR1-like immunoreactivity was seen at synaptic and non-synaptic sites on neuronal plasma membranes. Of 1514 NMDAR1-labeled profiles, 62% were dendrites and dendritic spines and the remainder were mainly unmyelinated axons and axon terminals. Sorcin-like immunoreactivity was present in 39% of the profiles that contained NMDAR1 labeling, most (533/595) of which were dendrites and dendritic spines. Of 1807 sorcin-labeled profiles, 42% were identified, however, as small processes including spine necks and unmyelinated axons or axon terminals. These profiles also occasionally contained NMDAR1 or showed synaptic or appositional contacts with other NMDAR1-immunoreactive neurons. The results of this study suggest that in the caudate-putamen nucleus, activation of NMDA receptors permits calcium influx at plasmalemmal sites mainly on dendrites where sorcin may play a role in calcium-induced calcium release. The presence of sorcin in some, but not all NMDA-containing neurons in the caudate-putamen nucleus has potential implications for the known differential vulnerability of certain striatal neurons to excitotoxins.