Original Research ARTICLE

Front. Syst. Neurosci., 11 May 2011 | doi: 10.3389/fnsys.2011.00028

Dissecting the contribution of individual receptor subunits to the enhancement of N-methyl-D-aspartate currents by dopamine D1 receptor activation in striatum

  • 1 Intellectual and Developmental Disabilities Research Center, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
  • 2 Department of Cell Biology, Duke University, Durham, NC, USA

Dopamine, via activation of D1 receptors, enhances N-methyl-D-aspartate (NMDA) receptor-mediated responses in striatal medium-sized spiny neurons. However, the role of specific NMDA receptor subunits in this enhancement remains unknown. Here we used genetic and pharmacological tools to dissect the contribution of NR1 and NR2A/B subunits to NMDA responses and their modulation by dopamine receptors. We demonstrate that D1 enhancement of NMDA responses does not occur or is significantly reduced in mice with genetic knock-down of NR1 subunits, indicating a critical role of these subunits. Interestingly, spontaneous and evoked α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptor-mediated responses were significantly enhanced in NR1 knock-down animals, probably as a compensatory mechanism for the marked reduction in NMDA receptor function. The NMDA receptor subunits NR2A and NR2B played differential roles in D1 modulation. Whereas genetic deletion or pharmacological blockade of NR2A subunits enhanced D1 potentiation of NMDA responses, blockade of NR2B subunits reduced this potentiation, suggesting that these regulatory subunits of the NMDA receptor counterbalance their respective functions. In addition, using D1 and D2 receptor EGFP-expressing mice, we demonstrate that NR2A subunits contribute more to NMDA responses in D1-MSSNs, whereas NR2B subunits contribute more to NMDA responses in D2 cells. The differential contribution of discrete receptor subunits to NMDA responses and dopamine modulation in the striatum has important implications for synaptic plasticity and selective neuronal vulnerability in disease states.

Keywords: NMDA, dopamine, receptor subunits, modulation, striatum

Citation: Jocoy EL, André VM, Cummings DM, Rao SP, Wu N, Ramsey AJ, Caron MG, Cepeda C and Levine MS (2011) Dissecting the contribution of individual receptor subunits to the enhancement of N-methyl-D-aspartate currents by dopamine D1 receptor activation in striatum. Front. Syst. Neurosci. 5:28. doi: 10.3389/fnsys.2011.00028

Received: 26 January 2011; Paper pending published: 26 March 2011;
Accepted: 28 April 2011; Published online: 11 May 2011.

Edited by:

Elizabeth Abercrombie, Rutgers-Newark: The State University of New Jersey, USA

Reviewed by:

Kuei Y. Tseng, Rosalind Franklin University of Medicine and Science, USA
Stephen Rayport, Columbia University, USA

Copyright: © 2011 Jocoy, André, Cummings, Rao, Wu, Ramsey, Caron, Cepeda and Levine. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Michael S. Levine, Intellectual and Developmental Disabilities Research Center, Semel Institute, Room 58-258, David Geffen School of Medicine, University of California Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, USA. e-mail: mlevine@mednet.ucla.edu

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