@article {Trantham-Davidson10652, author = {Heather Trantham-Davidson and Laurence C. Neely and Antonieta Lavin and Jeremy K. Seamans}, title = {Mechanisms Underlying Differential D1 versus D2 Dopamine Receptor Regulation of Inhibition in Prefrontal Cortex}, volume = {24}, number = {47}, pages = {10652--10659}, year = {2004}, doi = {10.1523/JNEUROSCI.3179-04.2004}, publisher = {Society for Neuroscience}, abstract = {Typically, D1 and D2 dopamine (DA) receptors exert opposing actions on intracellular signaling molecules and often have disparate physiological effects; however, the factors determining preferential activation of D1 versus D2 signaling are not clear. Here, in vitro patch-clamp recordings show that DA concentration is a critical determinant of D1 versus D2 signaling in prefrontal cortex (PFC). Low DA concentrations (\<500 nm) enhance IPSCs via D1 receptors, protein kinase A, and cAMP. Higher DA concentrations (\>1 μm) decrease IPSCs via the following cascade: D2{\textrightarrow}Gi{\textrightarrow}platelet-derived growth factor receptor{\textrightarrow}{\textuparrow}phospholipase C{\textrightarrow}{\textuparrow}IP3{\textrightarrow}{\textuparrow}Ca2+{\textrightarrow}{\textdownarrow}dopamine and cAMP-regulated phosphoprotein-32{\textrightarrow}{\textuparrow}protein phosphatase 1/2A{\textrightarrow}{\textdownarrow}GABAA. Blockade of any molecule in the D2-linked pathway reveals a D1-mediated increase in IPSCs, suggesting that D1 effects are occluded at higher DA concentrations by this D2-mediated pathway. Thus, DA concentration, by acting through separate signaling cascades, may determine the relative amount of cortical inhibition and thereby differentially regulate the tuning of cortical networks.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/24/47/10652}, eprint = {https://www.jneurosci.org/content/24/47/10652.full.pdf}, journal = {Journal of Neuroscience} }