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.

  • Article
  • Published:

Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity

An Erratum to this article was published on 01 December 2000

Abstract

To examine how functional circuits are established in the brain, we studied excitatory transmission in early postnatal hippocampus. Spontaneous neural activity was sufficient to selectively deliver GluR4-containing AMPA receptors (AMPA-Rs) into synapses. This delivery allowed non-functional connections to transmit at resting potentials and required NMDA receptors (NMDA-Rs) but not CaMKII activation. Subsequently, these delivered receptors were exchanged with non-synaptic GluR2-containing AMPA-Rs in a manner requiring little neuronal activity. The enhanced transmission resulting from this delivery and subsequent exchange was maintained for at least several days and required an interaction between GluR2 and NSF. Thus, this sequence of subunit-specific trafficking events triggered by spontaneous activity in early postnatal development may be crucial for initial establishment of long-lasting functional circuitry.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Expression of endogenous and recombinant GluR4 during early hippocampal development.
Figure 2: Synaptic delivery of recombinant GluR4.
Figure 3: Spontaneous activity delivers GluR4-GFP into synapses.
Figure 4: Delivery of GluR4-GFP to silent synapses.
Figure 5: Delivery of endogenous GluR4 into synapses.
Figure 6: Exchange of synaptic GluR4-GFP with endogenous GluR2-containing receptor maintains potentiated transmission.
Figure 7: Maintenance of enhanced transmission depends on interactions between GluR2 and NSF.

Similar content being viewed by others

References

  1. Ramon y Cajal, S. Histologie du System Nerveux de l'Homme et Vertebres (Instituto Ramon y Cajal, Madrid, 1911).

    Google Scholar 

  2. Goodman, C. S. & Shatz, C. J. Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72 Suppl., 77–98 (1993).

    Article  Google Scholar 

  3. O'Brien, R. J. et al. Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp. Neuron 23, 309–323 (1999).

    Article  CAS  Google Scholar 

  4. Scheiffele, P., Fan, J., Choih, J., Fetter, R. & Serafini, T. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101, 657–669 (2000).

    Article  CAS  Google Scholar 

  5. Cline, H. T., Wu, G. Y. & Malinow, R. In vivo development of neuronal structure and function . Cold Spring Harb. Symp. Quant. Biol. 61, 95–104 (1996).

    Article  CAS  Google Scholar 

  6. Dingledine, R., Borges, K., Bowie, D. & Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61 (1999).

    CAS  Google Scholar 

  7. Petralia, R. S. et al. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nat. Neurosci. 2, 31–36 (1999 ).

    Article  CAS  Google Scholar 

  8. Liao, D., Zhang, X., O'Brien, R., Ehlers, M. D. & Huganir, R. L. Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nat. Neurosci. 2 , 37–43 (1999).

    Article  CAS  Google Scholar 

  9. Wu, G., Malinow, R. & Cline, H. T. Maturation of a central glutamatergic synapse. Science 274, 972–976 ( 1996).

    Article  CAS  Google Scholar 

  10. Durand, G. M., Kovalchuk, Y. & Konnerth, A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71 –75 (1996).

    Article  CAS  Google Scholar 

  11. Isaac, J. T., Crair, M. C., Nicoll, R. A. & Malenka, R. C. Silent synapses during development of thalamocortical inputs. Neuron 18, 269–280 ( 1997).

    Article  CAS  Google Scholar 

  12. Shi, S. H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284 , 1811–1816 (1999).

    Article  CAS  Google Scholar 

  13. Hayashi, Y. et al. Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science 287, 2262–2267 (2000).

    Article  CAS  Google Scholar 

  14. Constantine-Paton, M. & Cline, H. T. LTP and activity-dependent synaptogenesis: the more alike they are, the more different they become. Curr. Opin. Neurobiol. 8, 139–148 (1998).

    Article  CAS  Google Scholar 

  15. Nishimune, A. et al. NSF binding to GluR2 regulates synaptic transmission. Neuron 21, 87–97 ( 1998).

    Article  CAS  Google Scholar 

  16. Osten, P. et al. The AMPA receptor GluR2 C terminus can mediate a reversible, ATP- dependent interaction with NSF and alpha- and beta-SNAPs. Neuron 21, 99–110 ( 1998).

    Article  CAS  Google Scholar 

  17. Song, I. et al. Interaction of the N-ethylmaleimide-sensitive factor with AMPA receptors. Neuron 21, 393– 400 (1998).

    Article  CAS  Google Scholar 

  18. Luthi, A. et al. Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction. Neuron 24, 389–399 (1999).

    Article  CAS  Google Scholar 

  19. Luscher, C. et al. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 24, 649– 658 (1999).

    Article  CAS  Google Scholar 

  20. Malinow, R. et al. in Imaging Neurons: A Laboratory Manual (eds. Yuste, R., Lanni, F. & Konnerth, A) 58.1–58.8 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1999).

    Google Scholar 

  21. Verdoorn, T. A., Burnashev, N., Monyer, H., Seeburg, P. H. & Sakmann, B. Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252, 1715–1718 (1991).

    Article  CAS  Google Scholar 

  22. Hestrin, S., Nicoll, R. A., Perkel, D. J. & Sah, P. Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J. Physiol. (Lond.) 422, 203–225 (1990).

    Article  CAS  Google Scholar 

  23. Ben-Ari, Y., Cherubini, E., Corradetti, R. & Gaiarsa, J. L. Giant synaptic potentials in immature rat CA3 hippocampal neurones. J. Physiol. (Lond.) 416, 303–325 (1989).

    Article  CAS  Google Scholar 

  24. Garaschuk, O., Hanse, E. & Konnerth, A. Developmental profile and synaptic origin of early network oscillations in the CA1 region of rat neonatal hippocampus. J. Physiol. (Lond.) 507, 219–236 (1998).

    Article  CAS  Google Scholar 

  25. Palva, J. M. et al. Fast network oscillations in the newborn rat hippocampus in vitro. J. Neurosci. 20, 1170– 1178 (2000).

    Article  CAS  Google Scholar 

  26. Margrie, T. W., Rostas, J. A. & Sah, P. Presynaptic long-term depression at a central glutamatergic synapse: a role for CaMKII. Nat. Neurosci. 1, 378–383 (1998).

    Article  CAS  Google Scholar 

  27. Lisman, J., Malenka, R. C., Nicoll, R. A. & Malinow, R. Learning mechanisms: the case for CaM-KII. Science 276, 2001–2002 (1997).

    Article  CAS  Google Scholar 

  28. Liao, D. & Malinow, R. Deficiency in induction but not expression of LTP in hippocampal slices from young rats. Learn. Mem. 3, 138–149 ( 1996).

    Article  CAS  Google Scholar 

  29. Liao, D., Hessler, N. A. & Malinow, R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400–404 ( 1995).

    Article  CAS  Google Scholar 

  30. O'Brien, R. J., Lau, L. F. & Huganir, R. L. Molecular mechanisms of glutamate receptor clustering at excitatory synapses. Curr. Opin. Neurobiol. 8, 364–369 (1998).

    Article  CAS  Google Scholar 

  31. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133– 1138 (1996).

    Article  CAS  Google Scholar 

  32. Ruthazer, E. S. & Stryker, M. P. The role of activity in the development of long-range horizontal connections in area 17 of the ferret. J. Neurosci. 16, 7253– 7269 (1996).

    Article  CAS  Google Scholar 

  33. Kim, H. G., Fox, K. & Connors, B. W. Properties of excitatory synaptic events in neurons of primary somatosensory cortex of neonatal rats. Cereb. Cortex 5, 148–157 ( 1995).

    Article  CAS  Google Scholar 

  34. Isaac, J. T., Nicoll, R. A. & Malenka, R. C. Evidence for silent synapses: implications for the expression of LTP. Neuron 15, 427– 434 (1995).

    Article  CAS  Google Scholar 

  35. Galli, L. & Maffei, L. Spontaneous impulse activity of rat retinal ganglion cells in prenatal life. Science 242 , 90–91 (1988).

    Article  CAS  Google Scholar 

  36. Weliky, M. & Katz, L. C. Correlational structure of spontaneous neuronal activity in the developing lateral geniculate nucleus in vivo. Science 285, 599–604 ( 1999).

    Article  CAS  Google Scholar 

  37. Bliss, T. V. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361 , 31–39 (1993).

    Article  CAS  Google Scholar 

  38. Zamanillo, D. et al. Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284, 1805–1811 (1999).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  40. 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).

    Article  CAS  Google Scholar 

  41. 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).

    Article  CAS  Google Scholar 

  42. Gomperts, S. N., Carroll, R., Malenka, R. C. & Nicoll, R. A. Distinct roles for ionotropic and metabotropic glutamate receptors in the maturation of excitatory synapses. J. Neurosci. 20, 2229–2237 (2000).

    Article  CAS  Google Scholar 

  43. Bekkers, J. M. & Stevens, C. F. Presynaptic mechanism for long-term potentiation in the hippocampus. Nature 346, 724–729 ( 1990).

    Article  CAS  Google Scholar 

  44. Liu, S. Q. & Cull-Candy, S. G. Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405, 454–458 (2000).

    Article  CAS  Google Scholar 

  45. Zhu, J. J. Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1 and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites. J. Physiol. (Lond.) 526, 571–587 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Song-Hai Shi for help in cloning GluR2-GFP and GluR3-GFP constructs, Nancy Dawkins-Pisani and Tamara Howard for technical assistance, and H. Cline, J. Huang, Z. Mainen, E. Ruthazer and members of the Malinow laboratory for comments and discussions. This study was supported by the NIH, the Alzheimer's Association and the NARSAD Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roberto Malinow.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, J., Esteban, J., Hayashi, Y. et al. Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity. Nat Neurosci 3, 1098–1106 (2000). https://doi.org/10.1038/80614

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/80614

This article is cited by

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