Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Differential regulation of synaptic and extra-synaptic NMDA receptors

Nature Neuroscience volume 5, pages 833–834 (2002)Cite this article

Abstract

A variety of processes limit NMDA (N-methyl-D-aspartate) receptor (NMDAR) activity in response to agonist exposure, including rundown—the decline of peak current with repeated, sustained agonist application1,2,3,4. Here we report that calcium and tyrosine phosphorylation differentially regulate rundown of synaptic versus extrasynaptic NMDAR-mediated current in rat hippocampal pyramidal neurons.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Synaptic NMDARs are more stable than extrasynaptic NMDARs.
Figure 2: Different mechanisms underlying Ca2+-independent and -dependent rundown.

Similar content being viewed by others

References

  1. Dingledine, R., Borges, K., Bowie, D. & Traynelis, S.F. Pharmacol. Rev. 51, 7–61 (1999).

    CAS  PubMed  Google Scholar 

  2. Vissel, B., Krupp, J.J., Heinemann, S.F. & Westbrook, G.L. Nat. Neurosci. 4, 587–596 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Wang, Y.T., Yu, X.M. & Salter, M.W. Proc. Natl. Acad. Sci. USA 93, 1721–1725 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rosenmund, C. & Westbrook, G.L. Neuron 10, 805–814 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Hollmann, M. & Heinemann, S. Annu. Rev. Neurosci. 17, 31–108 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Tovar, K.R. & Westbrook, G.L. J. Neurosci. 19, 4180–4188 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li, J.H. et al. Eur. J. Neurosci. 10, 1704–1715 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Rumbaugh, G. & Vicini, S. J. Neurosci. 19, 10603–10610 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Stocca, G. & Vicini, S. J. Physiol. (Lond.) 507, 13–24 (1998).

    Article  CAS  Google Scholar 

  10. Posner, B.I. et al. J. Biol. Chem. 269, 4596–4604 (1994).

    CAS  PubMed  Google Scholar 

  11. Chen, N., Luo, T. & Raymond, L.A. J. Neurosci. 19, 6844–6854 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Man, H.Y. et al. Neuron 25, 649–662 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Roche, K.W. et al. Nat. Neurosci. 4, 794–802 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Umemiya, M., Chen, N., Raymond, L.A. & Murphy, T.H. J. Neurosci. 21, 1–9 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Heart and Stroke Foundation (Doctoral Research Award, B.L.; operating grant, L.A.R.), Hereditary Disease Foundation (Postdoctoral Fellowship Award, N.C.) and the Canadian Institutes for Health Research (MOP-49586, T.H.M. and L.A.R.).

Author information

Authors and Affiliations

  1. Department of Psychiatry, Kinsmen Laboratory, University of British Columbia, Vancouver, V6T 1Z3, British Columbia, Canada

    Bo Li, Nansheng Chen, Tao Luo, Yo Otsu, Timothy H. Murphy & Lynn A. Raymond

Authors
  1. Bo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nansheng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tao Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yo Otsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Timothy H. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lynn A. Raymond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lynn A. Raymond.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1.

Rundown of peak current mediated by 2B-subtype differs from that of 2A-containing NMDARs. (GIF 17 kb)

(a) Representative responses evoked by NMDA recorded from neurons at 5 d.i.v. (upper), 14 d.i.v. with 10μM ifenprodil (middle), and 15 d.i.v. following isolation of 2B-subtype current by pre-treatment with 20μM MK-801 and 10μM ifenprodil (lower). (b) Pooled data showing development of rundown. Peak current amplitude was normalized to first response. (c) Responses of representative neurons to NMDA in zero Ca2+e. Recordings at +40 mV were made in external 1 mM Mg2+. (d) Pooled data showing Ca2+-independent rundown. Similar results were obtained using 1mM NMDA/100μM glycine to induce rundown (not shown).

Supplementary Fig. 2.

Immunofluorescence internalization assay of mature neurons. Live neurons (20 d.i.v.) were labeled with antibodies recognizing an extracellular region of NR1 and then treated with either control condition (salt solution), or NMDA (1 mM) + glycine (100 μM), for 10 min (see methods above). Representative neurons from n = 2 different experiments. (JPG 23 kb)

Supplementary Methods (PDF 36 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, B., Chen, N., Luo, T. et al. Differential regulation of synaptic and extra-synaptic NMDA receptors. Nat Neurosci 5, 833–834 (2002). https://doi.org/10.1038/nn912

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn912

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing