Skip to content

Advertisement

  • Poster presentation
  • Open Access

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

BMC Neuroscience20078 (Suppl 2) :P111

https://doi.org/10.1186/1471-2202-8-S2-P111

  • Published:

Keywords

  • Dopamine
  • NMDA Receptor
  • Positive Feedback System
  • Modeling Technique
  • Potential Contribution

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.

Authors’ Affiliations

(1)
Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, USA

References

  1. Cepeda C, Levine MS: Where do you think you are going? The NMDA-D1 receptor trap. Science STKE. 2006, 2006: pe20-10.1126/stke.3332006pe20.Google Scholar
  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. 10.1073/pnas.032654599.PubMedPubMed CentralView ArticleGoogle Scholar
  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. 10.1124/mol.65.1.121.PubMedView ArticleGoogle Scholar
  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.PubMedGoogle Scholar
  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. 10.1074/jbc.M213140200.PubMedView ArticleGoogle Scholar

Copyright

Advertisement