These authors contributed equally to this study.
Dopamine D1 receptor-mediated enhancement of NMDA receptor trafficking requires rapid PKC-dependent synaptic insertion in the prefrontal neurons
Article first published online: 31 MAR 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 114, Issue 1, pages 62–73, July 2010
How to Cite
Li, Y.-C., Liu, G., Hu, J.-L., Gao, W.-J. and Huang, Y.-Q. (2010), Dopamine D1 receptor-mediated enhancement of NMDA receptor trafficking requires rapid PKC-dependent synaptic insertion in the prefrontal neurons. Journal of Neurochemistry, 114: 62–73. doi: 10.1111/j.1471-4159.2010.06720.x
- Issue published online: 8 JUN 2010
- Article first published online: 31 MAR 2010
- Received January 20, 2010; revised manuscript received March 23, 2010; accepted March 24, 2010.
Vol. 124, Issue 6, 894, Article first published online: 3 MAR 2013
- D1 receptors;
- NMDA receptors;
- prefrontal cortex;
- psychiatric disorders
J. Neurochem. (2010) 114, 62–73.
Understanding the interaction between dopamine and glutamate, particularly the interaction of dopamine and NMDA receptors, may enable a more rational approach to the treatment of schizophrenia, drug addiction, and other psychiatric disorders. We show that, in prefrontal cortical neurons, dopamine D1-induced enhancement of NMDA receptor function depends on rapid insertion of new NMDA receptor 2B subunits on the synaptic surface. Protein kinase A (PKA) inhibitor, but not protein kinase C (PKC) inhibitor, completely blocked dopamine D1 agonist SKF-81297-induced increase of the total expression of NMDA receptors. Furthermore, SKF-81297 failed to alter the surface expression and synaptic insertion of NMDA receptors in the presence of PKA inhibitor, phospholipase C inhibitor, PKC inhibitor, or Src family kinase inhibitor. Our data suggest that D1-mediated enhancement of NMDA current depends on the NMDA receptor trafficking through rapid synaptic insertion and both PKA and PKC signaling pathways play important roles in the regulatory process. Although both PKA and PKC mediate the D1-induced enhancement of NMDA receptors, the phospholipase C-PKC-Src pathway is only required for surface expression and new synaptic insertion of NMDA receptors.