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.

Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo

Abstract

Sensory experience is crucial in the refinement of synaptic connections in the brain during development. It has been suggested that some forms of experience-dependent synaptic plasticity in vivo are associated with changes in the complement of postsynaptic glutamate receptors, although direct evidence has been lacking. Here we show that visual experience triggers the rapid synaptic insertion of new NMDA receptors in visual cortex. The new receptors have a higher proportion of NR2A subunits and, as a consequence, different functional properties. This effect of experience requires NMDA receptor activation and protein synthesis. Thus, rapid regulation of postsynaptic glutamate receptors is one mechanism for developmental plasticity in the brain. Changes in NMDA receptor expression provide a mechanism by which brief sensory experience can regulate the properties of NMDA receptor-dependent plasticity in visual cortex.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Visual experience regulates the composition of NMDARs in synaptoneurosomes from visual cortex.
Figure 2: The ifenprodil sensitivity of NMDAR-mediated field potentials in visual cortex is experience dependent.
Figure 3: Brief light exposure induces a rapid change in synaptic NMDAR composition and function in visual cortex.
Figure 4: Treatment of animals with CPP, a competitive antagonist of NMDARs, or cycloheximide, an inhibitor of mRNA translation, blocks the experience-induced increase in NR2A/B.

References

  1. Wyszynski, M. et al. Differential regional expression and ultrastructural localization of alpha-actinin-2, a putative NMDA receptor-anchoring protein, in rat brain. J. Neurosci. 18, 1383– 1392 (1998).

    CAS  Article  Google Scholar 

  2. Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B. & Seeburg, P. H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529–540 (1994).

    CAS  Article  Google Scholar 

  3. Ishii, T. et al. Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. J. Biol. Chem. 268, 2836–2843 (1993).

    CAS  PubMed  Google Scholar 

  4. Rostas, J. A. et al. Enhanced tyrosine phosphorylation of the 2B subunit of the N-methyl-D-aspartate receptor in long-term potentiation. Proc. Natl. Acad. Sci. USA 93, 10452–10456 (1996).

    CAS  Article  Google Scholar 

  5. Gingrich, M. B., Traynelis, S. F., Conn, P. J. & Zheng, F. Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition. Nat. Neurosci. 1, 185– 191 (1998).

    Article  Google Scholar 

  6. Lau, L. F. & Huganir, R. L. Differential tyrosine phosphorylation of N-methyl-D-aspartate receptor subunits. J. Biol. Chem. 270, 20036–20041 (1995).

    CAS  Article  Google Scholar 

  7. Kohr, G. & Seeburg, P. H. Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the src family. J. Physiol. (Lond.) 492, 445– 452 (1996).

    Article  Google Scholar 

  8. Sheng, M., Cummings, J., Rolden, L. A., Jan, Y. N. & Jan, L. Y. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 368, 144–147 (1994).

    CAS  Article  Google Scholar 

  9. Flint, A. C., Maisch, U. S., Weishaupt, J. H., Kriegstein, A. R. & Monyer, H. NR2A subunit expression shortens NMDA receptor synaptic currents in developing neocortex. J. Neurosci. 17, 2469–2476 (1997).

    CAS  Article  Google Scholar 

  10. Carmignoto, G. & Vicini, S. Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Science 258, 1007–1011 (1992).

    CAS  Article  Google Scholar 

  11. Hollingsworth, E. B. et al. Biochemical characterization of a filtered synaptoneurosome preparation from guinea pig cerebral cortex: cyclic adenosine 3´:5´-monophosphate-generating systems, receptors, and enzymes. J. Neurosci. 5, 2240–2253 (1985).

    CAS  Article  Google Scholar 

  12. Williams, K., Russell, S. L., Shen, Y. M. & Molinoff, P. B. Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. Neuron 10, 267–278 (1993).

    CAS  Article  Google Scholar 

  13. Church, J., Fletcher, E. J., Baxter, K. & MacDonald, J. F. Blockade by ifenprodil of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones: comparison with N- methyl-D-aspartate receptor antagonist actions. Br. J. Pharmacol. 113, 499–507 (1994).

    CAS  Article  Google Scholar 

  14. Gottmann, K., Mehrle, A., Gisselmann, G. & Hatt, H. Presynaptic control of subunit composition of NMDA receptors mediating synaptic plasticity. J. Neurosci. 17, 2766– 2774 (1997).

    CAS  Article  Google Scholar 

  15. Ramoa, A. S. & Prusky, G. Retinal activity regulates developmental switches in functional properties and ifenprodil sensitivity of NMDA receptors in the lateral geniculate nucleus. Dev. Brain. Res. 101, 165–175 (1997).

    CAS  Article  Google Scholar 

  16. Roberts, E. B., Meredith, M. A. & Ramoa, A. S. Suppression of NMDA receptor function using antisense DNA blocks ocular dominance plasticity while preserving visual responses. J. Neurophysiol. 80, 1021– 1032 (1998).

    CAS  Article  Google Scholar 

  17. Bear, M. F., Kleinschmidt, A., Gu, Q. & Singer, W. Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist. J. Neurosci. 10, 909–925 (1990).

    CAS  Article  Google Scholar 

  18. Lissin, D. V. et al. Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors. Proc. Natl. Acad. Sci. USA 95, 7097–7102 (1998).

    CAS  Article  Google Scholar 

  19. Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C. & Nelson, S. B. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391, 892–896 (1998).

    CAS  Article  Google Scholar 

  20. Ozaki, M., Sasner, M., Yano, R., Lu, H. S. & Buonanno, A. Neuregulin-beta induces expression of an NMDA-receptor subunit. Nature 390, 691– 694 (1997).

    CAS  Article  Google Scholar 

  21. Rao, A. & Craig, A. M. Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons. Neuron 19, 801–812 (1997).

    CAS  Article  Google Scholar 

  22. Craig, A. M. Activity and synaptic receptor targeting: the long view. Neuron 21, 459–462 (1998).

    CAS  Article  Google Scholar 

  23. Buisseret, P., Gary-Bobo, E. & Imbert, M. Ocular motility and recovery of orientational properties of visual cortical neurones in dark-reared kittens. Nature 272, 816–817 (1978).

    CAS  Article  Google Scholar 

  24. Buisseret, P., Gary-Bobo, E. & Imbert, M. Plasticity in the kitten's visual cortex: effects of the suppression of visual experience upon the orientational properties of visual cortical cells. Dev. Brain Res. 4, 417–426 (1982).

    Article  Google Scholar 

  25. Fox, K., Daw, N., Sato, H. & Czepita, D. Dark-rearing delays the loss of NMDA-receptor function in kitten visual cortex. Nature 350, 342–344 (1991).

    CAS  Article  Google Scholar 

  26. Wu, L. et al. CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of α-CaMKII mRNA at synapses. Neuron 21, 1129–1139 (1998).

    CAS  Article  Google Scholar 

  27. Miyashiro, K., Dichter, M. & Eberwine, J. On the nature and differential distribution of mRNAs in hippocampal neurites: implications for neuronal functioning. Proc. Natl. Acad. Sci. USA 91, 10800– 10804 (1994).

    CAS  Article  Google Scholar 

  28. Steward, O. mRNA localization in neurons: a multipurpose mechanism? Neuron 18, 9–12 (1997).

    CAS  Article  Google Scholar 

  29. Bear, M. F. & Malenka, R. C. Synaptic plasticity: LTP and LTD. Curr. Opin. Neurobiol. 4, 389– 399 (1994).

    CAS  Article  Google Scholar 

  30. Gold, J. I. & Bear, M. F. A model of dendritic spine Ca2+ concentration exploring possible bases for a sliding modification threshold. Proc. Natl. Acad. Sci. USA 91, 3941–3945 (1994).

    CAS  Article  Google Scholar 

  31. Kirkwood, A., Rioult, M. G. & Bear, M. F. Experience-dependent modification of synaptic plasticity in visual cortex. Nature 381, 526– 528 (1996).

    CAS  Article  Google Scholar 

  32. Bienenstock, E. L., Cooper, L. N. & Munro, P. W. Theory for the development of neuron selectivity: Orientation specificity and binocular interaction in visual cortex. J. Neurosci. 2, 32–48 (1982).

    CAS  Article  Google Scholar 

  33. Kirkwood, A., Dudek, S. M., Gold, J. T., Aizenman, C. D. & Bear, M. F. Common forms of synaptic plasticity in the hippocampus and neocortex in vitro. Science 260, 1518–1521 (1993).

    CAS  Article  Google Scholar 

  34. Paoletti, P., Ascher, P. & Neyton, J. High-affinity zinc inhibition of NMDA NR1-NR2A receptors. J. Neurosci. 17, 5711– 5725 (1997).

    CAS  Article  Google Scholar 

  35. Otani, S., Marshall, C. J., Tate, W. P., Goddard, G. V. & Abraham, W. C. Maintenance of long-term potentiation in rat dentate gyrus requires protein synthesis but not messenger RNA synthesis immediately post-tetanization. Neuroscience 28, 519–526 (1989).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The authors thank D. Olstein, A. Sekhar, E. Sklar and S. Meagher for assistance. This work was supported in part by grants from the Human Frontiers Science Program and the National Eye Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark F. Bear.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Quinlan, E., Philpot, B., Huganir, R. et al. Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo. Nat Neurosci 2, 352–357 (1999). https://doi.org/10.1038/7263

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/7263

Further reading

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