• cingulate cortex;
  • dual-label immunocytochemistry;
  • electron microscopy;
  • glutamate transmission;
  • reward;
  • striatum


Glutamatergic neurons within the deep layers of the prefrontal cortex and dopaminergic neurons of the substantia nigra pars compacta preferentially terminate in patch-like regions within the caudate putamen nucleus (CPN). Activation of dopamine D2 receptors is known to potently modulate striatal glutamatergic transmission and may play a role in reward-based motor learning. To determine the cellular substrate for D2-mediated regulation of prefrontal corticostriatal transmission in striatal patches, we combined anterograde transport of biotinylated dextran amine (BDA) with immunogold-silver labeling of a D2 receptor antipeptide antiserum in rat brain. Injections centered in deep layers of the dorsal part of the anterior cingulate cortex, one of the prefrontal cortical regions, produced varicose axonal BDA labeling in a patch-like distribution in the dorsomedial CPN. Electron microscopy showed that in these patch compartments, BDA labeling was present exclusively in axons and terminals (total number = 581), 9% of which contained detectable D2-like immunoreactivity. Thirty percent of the BDA-labeled terminals formed asymmetric excitatory synapses with dendritic spine heads, and the remainder were without recognizable junctions. The recipient spines were unlabeled or contained immunogold–silver particles for D2 receptors. A few of the D2-labeled spines also received convergent, often nonsynaptic contact from D2-labeled terminals resembling dopaminergic afferents. In addition, the corticostriatal terminals often apposed spiny and nonspiny neuronal profiles that contained D2 labeling. These results suggest that dopamine D2 receptors are strategically positioned for presynaptic and postsynaptic modulation of prefrontal corticostriatal excitation of spiny neurons in striatal patches. The findings have direct implications for D2-mediated control of reward-related motor learning. J. Comp. Neurol. 442:392–404, 2002. © 2002 Wiley-Liss, Inc.