AU  - Trantham-Davidson, Heather
AU  - Neely, Laurence C.
AU  - Lavin, Antonieta
AU  - Seamans, Jeremy K.
TI  - Mechanisms Underlying Differential D1 versus D2 Dopamine Receptor Regulation of Inhibition in Prefrontal Cortex
PT  - JOURNAL ARTICLE
DP  - 2004 Nov 24 
TA  - The Journal of Neuroscience 
PG  - 10652-10659 
VI  - 24 
IP  - 47 
4099 - http://www.jneurosci.org/content/24/47/10652.abstract 
4100 - http://www.jneurosci.org/content/24/47/10652.full 
SO - J. Neurosci. 2004 Nov 24; 24(47):10652-10659 
AID  - 10.1523/JNEUROSCI.3179-04.2004 [doi] 
AB  - 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→Gi→platelet-derived growth factor receptor→↑phospholipase C→↑IP3→↑Ca2+→↓dopamine and cAMP-regulated phosphoprotein-32→↑protein phosphatase 1/2A→↓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.