Presence of NMDA-type glutamate receptors in cingulate corticostriatal terminals and their postsynaptic targets

The glutamatergic projection from the anterior cingulate cortex to the medi al caudate-putamen nucleus (CPN) has been implicated in motor and cognitive functions, many of which are potently modulated by activation of N-methyl- D-aspartate subtype of glutamate receptors (NMDARs). To determine the funct ional sites for NMDAR activation within this circuitry we combined anterogr ade transport of biotinylated dextran amine (BDA) from deep layers of the r at anterior cingulate cortex with immunogold labeling of NMDAR subunit, NMD AR1, in the dorsomedial CPN. BDA-containing axons were seen in patch-like c lusters in a neuropil that showed more uniform immunogold-silver labeling f or NMDAR1. Electron microscopy of these regions showed that BDA-labeling wa s present exclusively in axons and terminals, 23% (98 of 421) of which also contained NMDAR1-immunoreactivity (IR). BDA-labeled terminals often appose d NMDAR1-immunoreactive neuronal and glial profiles. These terminals also f ormed asymmetric excitatory-type synapses with dendritic spines. Of 155 ant erogradely labeled axon terminals forming asymmetric synapses, 34% were wit h NMDAR1-labeled, and 66% with unlabeled dendritic spines. These results pr ovide ultrastructural evidence for the involvement of NMDARs in presynaptic regulation of glutamate transmission, and in postsynaptic modulation of th e excitability of spiny neurons in patch-like compartments of the dorsomedi al CPN. These dual NMDAR-mediated actions are likely to play a major role i n the acquisition of new behaviors and reward-related processes that have b een associated with cortical input to the striatal patch compartments. Syna pse 35:300-310, 2000. (C) 2000 Wiley-Liss, Inc.