Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex.

Interactions between dopamine and N-methyl-D-aspartate receptors (NMDARs) in prefrontal cortex (PFC) and other brain regions are believed to play an important role in normal mental function and neuropsychiatric disorders. In this study, we examined the regulation of NMDAR currents by the dopamine D1 receptor in PFC pyramidal neurons. Application of the D1 receptor agonist SKF81297 caused a prominent increase of the steady-state NMDA-evoked current in acutely isolated PFC pyramidal neurons. The D1 effect on NMDARs was independent of protein kinase A or protein phosphatase 1, but was abolished by incubation of neurons in Ca2+-free medium. Intracellular application of the Ca2+ chelator, calmodulin, or calmodulin inhibitors largely prevented the D1 modulation of NMDAR currents. Moreover, inhibiting PKC activity or disrupting PKC association with its anchoring protein also significantly reduced the D1 effect on NMDAR currents. This upregulation of NMDAR activity by dopamine D1 receptors and the previous finding on up-regulation of dopamine D1 receptors by NMDAR activation provide a cellular mechanism for the reciprocal interactions between D1 and NMDARs. These interactions may play an important role in modulating synaptic plasticity and thus in cognitive and emotional processes.

[1]  P. Goldman-Rakic,et al.  Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys , 1994, Psychopharmacology.

[2]  R. Roth,et al.  The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia , 1999, Neuropsychopharmacology.

[3]  P. Greengard,et al.  A Dopamine/D1 Receptor/Protein Kinase A/Dopamine- and cAMP-Regulated Phosphoprotein (Mr 32 kDa)/Protein Phosphatase-1 Pathway Regulates Dephosphorylation of the NMDA Receptor , 1998, The Journal of Neuroscience.

[4]  J. Coyle,et al.  Glutamatergic mechanisms in schizophrenia. , 2003, Annual review of pharmacology and toxicology.

[5]  P. Goldman-Rakic,et al.  Modulation of memory fields by dopamine Dl receptors in prefrontal cortex , 1995, Nature.

[6]  P. Goldman-Rakic.  Working memory dysfunction in schizophrenia. , 1994, The Journal of neuropsychiatry and clinical neurosciences.

[7]  R. Huganir,et al.  Calmodulin Mediates Calcium-Dependent Inactivation of N-Methyl-D-Aspartate Receptors , 1998, Neuron.

[8]  M. Sheng,et al.  Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex. , 1999, Science.

[9]  D. Javitt,et al.  Recent advances in the phencyclidine model of schizophrenia. , 1991, The American journal of psychiatry.

[10]  Richard L. Huganir,et al.  Glutamate receptor phosphorylation and synaptic plasticity , 1994, Current Opinion in Neurobiology.

[11]  Streichenwein Sm,et al.  Am J Psychiatry , 1996 .

[12]  R. Wenthold,et al.  Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  Y. Khan,et al.  Cellular distribution of dopamine D1 and D2 receptors in rat medial prefrontal cortex , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  D. Trentham,et al.  Mechanism of 2-chloro-(epsilon-amino-Lys75)-[6-[4-(N,N- diethylamino)phenyl]-1,3,5-triazin-4-yl]calmodulin interactions with smooth muscle myosin light chain kinase and derived peptides. , 1994, Biochemistry.

[15]  Philip R. Cohen,et al.  Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1 , 1997, The EMBO journal.

[16]  P. Greengard,et al.  D(1) dopamine receptor activation reduces GABA(A) receptor currents in neostriatal neurons through a PKA/DARPP-32/PP1 signaling cascade. , 2000, Journal of neurophysiology.

[17]  C. Gonzalez-Islas,et al.  Dopamine Enhances EPSCs in Layer II–III Pyramidal Neurons in Rat Prefrontal Cortex , 2003, The Journal of Neuroscience.

[18]  P S Goldman-Rakic,et al.  D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Hans Forssberg,et al.  Selective up-regulation of dopamine D1 receptors in dendritic spines by NMDA receptor activation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Christian Rosenmund,et al.  Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons. , 1995, Journal of neurophysiology.

[21]  N. Andreasen,et al.  Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naïve patients , 1997, The Lancet.

[22]  David A Lewis,et al.  Catching Up on Schizophrenia Natural History and Neurobiology , 2000, Neuron.

[23]  A. Kyrozis,et al.  Ca(2+)‐dependent inactivation of NMDA receptors: fast kinetics and high Ca2+ sensitivity in rat dorsal horn neurons. , 1996, The Journal of physiology.

[24]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[25]  H. E. Rosvold,et al.  Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. , 1979, Science.

[26]  R. Dingledine,et al.  The glutamate receptor ion channels. , 1999, Pharmacological reviews.

[27]  B. Pitt.  Psychopharmacology , 1968, Mental Health.

[28]  R. Huganir,et al.  Characterization of Protein Kinase A and Protein Kinase C Phosphorylation of the N-Methyl-D-aspartate Receptor NR1 Subunit Using Phosphorylation Site-specific Antibodies* , 1997, The Journal of Biological Chemistry.

[29]  B. Orser,et al.  In CA1 Pyramidal Neurons of the Hippocampus Protein Kinase C Regulates Calcium-Dependent Inactivation of NMDA Receptors , 2000, The Journal of Neuroscience.

[30]  P. Greengard,et al.  Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP–32 and spinophilin , 1999, Nature Neuroscience.

[31]  P. Goldman-Rakic.  Cellular basis of working memory , 1995, Neuron.

[32]  R. Huganir,et al.  Inactivation of NMDA Receptors by Direct Interaction of Calmodulin with the NR1 Subunit , 1996, Cell.

[33]  J. Scott,et al.  Regulation of the AKAP79-Protein Kinase C Interaction by Ca2+/Calmodulin* , 1997, The Journal of Biological Chemistry.

[34]  P. Greengard,et al.  Beyond the Dopamine Receptor: Review the DARPP-32/Protein Phosphatase-1 Cascade , 1999 .

[35]  P S Goldman-Rakic,et al.  The “Psychic” Neuron of the Cerebral Cortex , 1999, Annals of the New York Academy of Sciences.

[36]  Ping Zhong,et al.  Regulation of NMDA Receptors by Dopamine D4 Signaling in Prefrontal Cortex , 2003, The Journal of Neuroscience.

[37]  R. Hales,et al.  J Neuropsychiatry Clin Neurosci , 1992 .

[38]  L. Langeberg,et al.  Coordination of Three Signaling Enzymes by AKAP79, a Mammalian Scaffold Protein , 1996, Science.

[39]  G. Westbrook,et al.  Interactions of Calmodulin and α-Actinin with the NR1 Subunit Modulate Ca2+-Dependent Inactivation of NMDA Receptors , 1999, The Journal of Neuroscience.

[40]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[41]  I. Módy,et al.  Regulation of NMDA channel function by endogenous Ca2+-dependent phosphatase , 1994, Nature.

[42]  Zhen Yan,et al.  Serotonin Receptors Modulate GABAA Receptor Channels through Activation of Anchored Protein Kinase C in Prefrontal Cortical Neurons , 2001, The Journal of Neuroscience.

[43]  Marc G Caron,et al.  Mice with Reduced NMDA Receptor Expression Display Behaviors Related to Schizophrenia , 1999, Cell.

[44]  A Carlsson,et al.  Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. , 2001, Annual review of pharmacology and toxicology.