D-1 DOPAMINE-RECEPTOR IMMUNOREACTIVITY IN HUMAN AND MONKEY CEREBRAL-CORTEX - PREDOMINANT AND EXTRASYNAPTIC LOCALIZATION IN DENDRITIC SPINES

Antibodies to the D-1 dopamine receptor were used to localize this protein in several areas of human and monkey. cerebral cortex with light and electron microscopy. In addition to cell body labeling in monkeys, all areas of humans and monkeys had a neuropil label with a laminar distribution predicted by previous D-1 receptor autoradiography studies. Using electron microscopy, this neuropil label was seen in numerous dendritic spines, in dendritic shafts, and in occasional axon terminals. While labeled spines were common, they represented only a subset of all cortical spines. Serial sectioning through labeled spines showed that the diaminobenzidine reaction product was usually not at postsynaptic densities but instead was displaced to the side of the large asymmetric (presumed glutamatergic) synapse. Furthermore, most labeled spines did not receive synapses with dopaminergic features, suggesting that many D-1 receptors are at extrasynaptic sites, possibly receiving dopamine via diffusion in the neuropil. Similarly, double labeling failed to reveal D-1 labeling at synapses of tyrosine hydroxylase immunoreactive axons. Localization to numerous dendritic spines suggests that a primary role of D-1 receptors is modulation of glutamatergic input to cortical pyramidal cells.