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This article is part of the supplement: Sixteenth Annual Computational Neuroscience Meeting: CNS*2007

Open Access Poster presentation

Physical interactions between D1 and NMDA receptors as a possible inhibitory mechanism to avoid excessive NMDA currents

Daniel B Smith, Lawrence C Udeigwe and Jonathan Rubin*

Author Affiliations

Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, USA

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BMC Neuroscience 2007, 8(Suppl 2):P111  doi:10.1186/1471-2202-8-S2-P111


The electronic version of this article is the complete one and can be found online at:


Published:6 July 2007

© 2007 Smith et al; licensee BioMed Central Ltd.

Poster presentation

Coactivation of N-methyl-D-aspartate (NMDA) and dopamine (DA) receptors generates a potentially feed-forward system that could lead to excessive NMDA currents [1]. Through second messenger systems, activation of NMDA receptors increases the presence of the D1 subtype of DA receptors in dendritic spines in striatum [2]. Likewise, activation of D1 receptors increases the number of NMDA receptors in synaptic regions in striatum [3,4]. Given the potential contribution of NMDA receptor activation to apoptosis, there must be some mechanism to limit the expression of NMDA currents. This mechanism is not yet currently known, however. Cepeda and Levine [1] have suggested that physical interactions may serve as a limiting mechanism to this positive feedback system. It is known that physical interactions between D1 and NMDA receptors may lead to formation of D1/NMDA complexes and may inhibit NMDA currents [5]. We use both dynamical systems and agent-based modeling techniques to investigate whether such physical interactions are sufficient to generate a stable fixed point for NMDA current levels or, more generally, to bound NMDA currents.

References

  1. Cepeda C, Levine MS: Where do you think you are going? The NMDA-D1 receptor trap.

    Science STKE 2006, 2006:pe20. Publisher Full Text OpenURL

  2. Scott L, Kruse MS, Forssberg H, Brismar H, Greengard P, Aperia A: Selective up-regulation of dopamine D1 receptors in dendritic spines by NMDA receptor activation.

    Proc Natl Acad Sci USA 2002, 99:1661-1664. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  3. Dunah AW, Sirianni AC, Fienberg AA, Bastia E, Schwarzschild MA, Standaert DG: Dopamine D1-dependent trafficking of striatal N-methyl-D-aspartate glutamate receptors requires Fyn protein tyrosine kinase but not DARPP-32.

    Mol Pharmacol 2004, 65:121-129. PubMed Abstract | Publisher Full Text OpenURL

  4. Dunah AW, Standaert DG: Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane.

    J Neurosci 2001, 21:5546-5558. PubMed Abstract | Publisher Full Text OpenURL

  5. Fiorentini C, Gardoni F, Spano P, Di Luca M, Missale C: Regulation of dopamine D1 receptor trafficking and desensitization by oligomerization with glutamate N-methyl-D-aspartate receptors.

    J Biol Chem 2003, 278:20196-20202. PubMed Abstract | Publisher Full Text OpenURL