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:

Postsynaptic conversion of silent synapses during LTP affects synaptic gain and transmission dynamics

Nature Neuroscience volume 4, pages 989–996 (2001)Cite this article

Abstract

Synaptic transmission relies on both the gain and the dynamics of synapses. Activity-dependent changes in synaptic gain are well-documented at excitatory synapses and may represent a substrate for information storage in the brain. Here we examine the mechanisms of changes in transmission dynamics at excitatory synapses. We show that paired-pulse ratios (PPRs) of AMPAR and NMDAR EPSCs onto dentate gyrus granule cells are often different; this difference is reduced during LTP, reflecting PPR changes of AMPAR but not NMDAR EPSCs. Presynaptic manipulations, however, produce parallel changes in AMPAR and NMDAR EPSCs. LTP at these synapses reflects a reduction in the proportion of silent synapses lacking functional AMPARs. Changes in PPR during LTP therefore reflect the initial difference between PPRs of silent and functional synapses. Functional conversion of silent synapses permits postsynaptic sampling from additional release sites and thereby affects the dynamics and gain of signals conveyed between 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: Non-identical paired-pulse ratios of AMPAR- and NMDAR-mediated EPSCs in dentate gyrus granule cells.
Figure 2: Pairing-induced LTP is associated with changes in paired-pulse ratios of AMPAR but not NMDAR EPSCs.
Figure 3: The amplitude and paired-pulse ratios of AMPAR and NMDAR EPSCs are similarly affected by presynaptic manipulations.
Figure 4: Pairing-induced LTP at perforant path synapses leads to a reduction of failure rate of AMPAR but not NMDAR EPSCs.
Figure 5: LTP-induced changes in paired-pulse ratios depend on the initial differences of PPR and failure rates between AMPAR and NMDAR EPSCs.
Figure 6: LTP-induced changes in transmission dynamics during repetitive stimulation.

Similar content being viewed by others

References

  1. Lisman, J. E. Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci. 20, 38–43 (1997).

    Article  CAS  Google Scholar 

  2. Ranck, J. B. Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. Exp. Neurol. 41, 461–531 (1973).

    Article  Google Scholar 

  3. Fox, S. E. & Ranck, J. B. Localization and anatomical identification of theta and complex spike cells in dorsal hippocampal formation of rats. Exp. Neurol. 49, 299–313 (1975).

    Article  CAS  Google Scholar 

  4. Manabe, T., Wyllie, D. J., Perkel, D. J. & Nicoll, R. A. Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus. J. Neurophysiol. 70, 1451–1459 (1993).

    Article  CAS  Google Scholar 

  5. Schulz, P. E., Cook, E. P. & Johnston, D. Changes in paired-pulse facilitation suggest presynaptic involvement in long-term potentiation. J. Neurosci. 14, 5325–5337 (1994).

    Article  CAS  Google Scholar 

  6. Debanne, D., Guérineau, N. C., Gähwiler, B. H. & Thompson, S. M. Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release. J. Physiol. (Lond.) 491, 163–176 (1996).

    Article  CAS  Google Scholar 

  7. Stevens, C. F. & Wang, Y. Facilitation and depression at single central synapses. Neuron 14, 795–802 (1995).

    Article  CAS  Google Scholar 

  8. Mennerick, S. & Zorumski, C. F. Paired-pulse modulation of fast excitatory synaptic currents in microcultures of rat hippocampal neurons. J. Physiol. (Lond.) 488, 85–101 (1995).

    Article  CAS  Google Scholar 

  9. Rosenmund, C., Clements, J. D. & Westbrook, G. L. Nonuniform probability of glutamate release at a hippocampal synapse. Science 262, 754–757 (1993).

    Article  CAS  Google Scholar 

  10. Hessler, N. A., Shirke, A. M. & Malinow, R. The probability of transmitter release at a mammalian central synapse. Nature 366, 569–572 (1993).

    Article  CAS  Google Scholar 

  11. Abbott, L. F., Varela, J. A., Sen, K. & Nelson, S. B. Synaptic depression and cortical gain control. Science 275, 220–224 (1997).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Malenka, R. C. & Nicoll, R. A. Long-term potentiation: a decade of progress? Science 285, 1870–1874 (1999).

    Article  CAS  Google Scholar 

  14. Malinow, R., Mainen, Z. F. & Hayashi, Y. LTP mechanisms: from silence to four-lane traffic. Curr. Opin. Neurobiol. 10, 352–357 (2000)

    Article  CAS  Google Scholar 

  15. Schulz, P. E. Long-term potentiation involves increases in the probability of neurotransmitter release. Proc. Natl. Acad. Sci. USA 94, 5888–5893 (1997).

    Article  CAS  Google Scholar 

  16. Markram, H. & Tsodyks, M. Redistribution of synaptic efficacy between neocortical pyramidal neurons. Nature 382, 807–810 (1996).

    Article  CAS  Google Scholar 

  17. Selig, D. K., Nicoll, R. A. & Malenka, R.C. Hippocampal long-term potentiation preserves the fidelity of postsynaptic responses to presynaptic bursts. J. Neurosci. 19, 1236–1246 (1999).

    Article  CAS  Google Scholar 

  18. Muller, D. & Lynch, G. Long-term potentiation differentially affects two components of synaptic responses in hippocampus. Proc. Natl. Acad. Sci. USA 85, 9346–9350 (1998).

    Article  Google Scholar 

  19. Kullmann, D. M. Amplitude fluctuations of dual-component EPSCs in hippocampal pyramidal cells: implications for long-term potentiation. Neuron 12, 1111–1120 (1994).

    Article  CAS  Google Scholar 

  20. Colino, A. & Malenka, R. C. Mechanisms underlying induction of long-term potentiation in rat medial and lateral perforant paths in vitro. J. Neurophysiol. 69, 1150–1159 (1993).

    Article  CAS  Google Scholar 

  21. 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 

  22. 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 

  23. Clark, K. A., Randall, A. D. & Collingridge G. L. A comparison of paired-pulsed facilitation of AMPA and NMDA receptor-mediated excitatory postsynaptic currents in the hippocampus. Exp. Brain Res. 101, 272–278 (1994).

    Article  CAS  Google Scholar 

  24. Buonomano, D. V. & Merzenich, M. M. Associative synaptic plasticity in hippocampal CA1 neurons is not sensitive to unpaired presynaptic activity. J. Neurophysiol. 76, 631–636 (1996).

    Article  CAS  Google Scholar 

  25. Kleschevnikov, A. M. et al. Changes in paired-pulse facilitation correlate with induction of long-term potentiation in area CA1 of rat hippocampal slices. Neuroscience 76, 829–843 (1997).

    Article  CAS  Google Scholar 

  26. Prince, D. A. & Stevens, C. F. Adenosine decreases neurotransmitter release at central synapses. Proc. Natl. Acad. Sci. USA 89, 8586–8590 (1992).

    Article  CAS  Google Scholar 

  27. Perkel, D. J. & Nicoll, R. A. Evidence for all-or-none regulation of neurotransmitter release: implications for long-term potentiation. J. Physiol. (Lond.) 471, 481–500 (1993).

    Article  CAS  Google Scholar 

  28. 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 

  29. Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545–559 (1998).

    Article  CAS  Google Scholar 

  30. Min, M. Y., Asztely, F., Kokaia, M. & Kullmann, D.M. Long-term potentiation and dual-component quantal signaling in the dentate gyrus. Proc. Natl. Acad. Sci. USA 95, 4702–4707 (1998).

    Article  CAS  Google Scholar 

  31. Malinow, R. Transmission between pairs of hippocampal slice neurons: quantal levels, oscillations, and LTP. Science 252, 722–724 (1991).

    Article  CAS  Google Scholar 

  32. Connors, B. W. & Gutnick, M. J. Intrinsic firing patterns of diverse neocortical neurons. Trends Neurosci. 13, 99–104 (1990).

    Article  CAS  Google Scholar 

  33. Wilson, M. A. & McNaughton, B. L. Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993).

    Article  CAS  Google Scholar 

  34. Gerstner, W., Kreiter, A. K., Markram, H. & Herz, A. V. Neural codes: firing rates and beyond. Proc. Natl. Acad. Sci. USA 94, 12740–12741 (1997).

    Article  CAS  Google Scholar 

  35. Racca, C., Stephenson, F. A., Streit, P., Roberts, J. D. & Somogyi, P. NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area. J. Neurosci. 20, 2512–2522 (2000).

    Article  CAS  Google Scholar 

  36. Takumi, Y., Ramirez-Leon, V., Laake, P., Rinvik, E. & Ottersen, O. P. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat. Neurosci. 2, 618–624 (1999).

    Article  CAS  Google Scholar 

  37. Pierce, J. P. & Lewin, G. R. An ultrastructural size principle. Neuroscience 58, 441–446 (1994).

    Article  CAS  Google Scholar 

  38. Schikorski, T. & Stevens, C. F. Quantitative fine-structural analysis of olfactory cortical synapses. Proc. Natl. Acad. Sci. USA 96, 4107–4112 (1999).

    Article  CAS  Google Scholar 

  39. Gasparini, S., Saviane, C., Voronin, L. L. & Cherubini, E. Silent synapses in the developing hippocampus: lack of functional AMPA receptors or low probability of glutamate release? Proc. Natl. Acad. Sci. USA 97, 9741–9746 (2000).

    Article  CAS  Google Scholar 

  40. Davis, G. W. & Murphey, R. K. Long-term regulation of short-term transmitter release properties: retrograde signaling and synaptic development. Trends Neurosci. 17, 9–13 (1994).

    Article  CAS  Google Scholar 

  41. Markram, H., Wang, Y. & Tsodyks, M. Differential signaling via the same axon of neocortical pyramidal neurons. Proc. Natl. Acad. Sci. USA 95, 5323–5328 (1998).

    Article  CAS  Google Scholar 

  42. Reyes, A. et al. Target-cell-specific facilitation and depression in neocortical circuits. Nat. Neurosci. 1, 279–285 (1998).

    Article  CAS  Google Scholar 

  43. Mainen, Z. F., Malinow, R. & Svoboda, K. Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated. Nature 399, 151–155 (1999).

    Article  CAS  Google Scholar 

  44. Wang, J. H. & Kelly, P. T. Attenuation of paired-pulse facilitation associated with synaptic potentiation mediated by postsynaptic mechanisms. J. Neurophysiol. 78, 2707–2716 (1997).

    Article  CAS  Google Scholar 

  45. Katz, B. & Miledi, R. The role of calcium in neuromuscular facilitation. J. Physiol. (Lond.) 195, 481–492 (1968).

    Article  CAS  Google Scholar 

  46. Christie, B. R. & Abraham, W. C. Differential regulation of paired-pulse plasticity following LTP in the dentate gyrus. Neuroreport 5, 385–388 (1994).

    Article  CAS  Google Scholar 

  47. Schulz, P. E. & Fitzgibbons, J. C. Differing mechanisms of expression for short- and long-term potentiation. J. Neurophysiol. 78, 321–334 (1997).

    Article  CAS  Google Scholar 

  48. Volgushev, M., Voronin, L. L., Chistiakova, M. & Singer, W. Relations between long-term synaptic modifications and paired-pulse interactions in the rat neocortex. Eur. J. Neurosci. 9, 1656–1665 (1997).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank N. Dawkins-Pisani for technical assistance, and R. Miles and Z. Mainen for reading the manuscript. This work was supported by the Human Frontier Science Program Organization (J.C.P.), the Mathers Foundation and NIH (R.M.).

Author information

Author notes

  1. J. C. Poncer & R. Malinow

    Present address: CNRS FRE2199, Université René Descartes, 45, rue des Saints Pères, Paris, 75006, France

Authors and Affiliations

  1. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, 11724, New York, USA

    J. C. Poncer & R. Malinow

  2. INSERM U261, Institut Pasteur, 25 rue du Dr. Roux, Paris, 75015, France

    J. C. Poncer

Authors
  1. J. C. Poncer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Malinow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. C. Poncer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Poncer, J., Malinow, R. Postsynaptic conversion of silent synapses during LTP affects synaptic gain and transmission dynamics. Nat Neurosci 4, 989–996 (2001). https://doi.org/10.1038/nn719

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn719

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