Dopamine D1 and N-methyl-D-aspartate receptor interactions in rat prefrontal cortex: physical and physiological relationship.

KRUSE MS, JAY T

San Diego, CA

Congreso; Society for Neuroscience 37th Annual Meeting; 2007

Society for Neuroscience

Dopamine, via stimulation of D1 receptors in the prefrontal cortex is involved in high cognitive functions (working memory, attention) and also required for NMDA-mediated long-term potentiation at hippocampal to prefrontal synapses. Despite the tremendous importance of D1 receptors in prefrontal plasticity, little is known about the molecular mechanisms underlying D1-NMDA receptors interactions.Here, we show that D1 receptors and the NMDA receptor subunit NR1 co-localize in single pyramidal neurons and interneurons of rat prefrontal cortex. NR1 expression is predominantly found in neuronal branches and somatic cell membrane of different cell types. On the other hand, D1 receptor is predominantly found in the cell soma and less frequently in branches of pyramidal-like cells and parvalbumin positive cells. In addition, NR1 co-immunoprecipitates with D1 receptor in adult medial prefrontal cortex, suggesting that the receptors are co-clustered in this structure. We studied the physiological significance of this interaction. NMDA did not affect the cAMP production induced by D1 receptor activation. In contrast, treatment with the D1 receptor agonist SKF 38393 potentiated the NMDA mediated Ca2+ influx. In the presence of the PKA inhibitor H-89, D1 receptor was unable to upregulate the Ca2+ influx by NMDA. We conclude that D1 receptor potentiates the NMDA-Ca2+ signal by activation of the PKA signalling cascade. Together these results will increase the understanding of D1-NMDA receptor interaction in the prefrontal cortex. Such interaction is crucial since the balance between D1 and NMDA receptors in prefrontal cortex plays a potential role in specific physiological and pathological processes.