Abstract
D1 family receptors (D1R) in prefrontal cortex (PFC) are critical for normal cognition and are implicated in pathological states such as schizophrenia. The two D1R subtypes, D1 and D5, cannot be pharmacologically distinguished but have important functional differences. To understand their contributions to cortical function, we quantified their localization in the neuropil of primate PFC. We identified different patterns of distribution for the two receptors that showed variation across cortical laminae. Although D1 was enriched in spines and D5 in dendrites, there was considerable overlap in their distribution within neuronal compartments. To determine whether the D1 and D5 receptors are localized to separate populations of synapses, we employed double-labeling methods. We found the two receptors colocalized and quantified the overlap of their distribution in spines and axon terminals of prefrontal cortical area 9 in the Macaca mulatta monkey. The two receptors are found in partially overlapping populations, such that the D5 receptor is found in a subpopulation of those spines and terminals that contain D1. These results indicate that dopamine activation of the two D1R subtypes does not modulate disparate populations of synapses onto dendritic spines in prefrontal cortical area 9; rather, dopamine can activate D1 and D5 receptors on the same spines, plus an additional group of spines that contains only D1. The implications of these results for the dose-dependent relationship between D1R activation and PFC function are discussed.