Phosphatidylinositol-linked novel D1 dopamine receptor facilitates long-term depression in rat hippocampal CA1 synapses

Recent work has demonstrated that a phosphatidylinositol (PI)-linked D1 dopamine receptor selective agonist, SKF83959, mediates phosphatidylinositol hydrolysis via activation of phospholipase Cβ in brain. Specific contributions of SKF83959 to synaptic plasticity have not been well elucidated. The aim of the current investigation was to characterize the role of SKF83959 on long-term depression (LTD) in the CA1 region of rat hippocampal slices and to explore the molecular events leading to these changes. The results indicated that SKF83959 stimulation significantly depressed field excitatory postsynaptic potentials (fEPSPs) in a dose-dependent manner and facilitated the induction of LTD by LFS. SKF83959-facilitated LTD required activation of phospholipase C (PLC). NMDA receptors were involved in this response. Calcium chelator, BAPTA-AM prevented SKF83959-facilitated LTD, indicating that cytosolic free calcium concentration ([Ca2+]i) elevation could account for this response. Furthermore, SKF83959-facilitated LTD was significantly depressed in the presence of calcineurin (PP2B) inhibitors cyclosporin A (CsA) and associated with a persistent increase in the expression of calcineurin A. Taken together, these findings demonstrate a novel role for PI-linked D1 dopamine receptor in the neuromodulation of hippocampal LTD.