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Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice

Abstract

LONG-TERM potentiation (LTP) is an enhancement of synaptic strength that can be produced by pairing of presynaptic activity with postsynaptic depolarization1. LTP in the hippocampus has been extensively studied as a cellular model of learning and memory, but the nature of the underlying synaptic modification remains elusive, partly because our knowledge of central synapses is still limited2,3. One proposal4,5 is that the modification is postsynaptic, and that synapses expressing only NMDA (N-methyl-D-aspartate) receptors before potentiation are induced by LTP to express functional AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors. Here we report that a high proportion of synapses in hippocampal area CA1 transmit with NMDA receptors but not AMPA receptors, making these synapses effectively non-functional at normal resting potentials. These silent synapses acquire AMPA-type responses following LTP induction. Our findings challenge the view6–10 that LTP in CA1 involves a presynaptic modification, and suggest instead a simple postsynaptic mechanism for both induction and expression of LTP.

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References

  1. Bliss, T. V. P. & Collingridge, G. L. Nature 361, 31–39 (1993).

    Article  ADS  CAS  Google Scholar 

  2. Edwards, F. Nature 350, 271–272 (1991).

    Article  ADS  CAS  Google Scholar 

  3. Malinow, R. Science 266, 1195–1196 (1994).

    Article  ADS  CAS  Google Scholar 

  4. Liao, D., Jones, A. & Malinow, R. Neuron 9, 1089–1097 (1992).

    Article  CAS  Google Scholar 

  5. Kullmann, D. M. Neuron 12, 1111–1120 (1994).

    Article  CAS  Google Scholar 

  6. Malinow, R. & Tsien, R. W. Nature 346, 177–180 (1990).

    Article  ADS  CAS  Google Scholar 

  7. Voronin, L. L. Neuroscience 56, 275–304 (1993).

    Article  CAS  Google Scholar 

  8. Kullman, D. M. & Nicoll, R. A. Nature 357, 240–244 (1992).

    Article  ADS  Google Scholar 

  9. Larkman, A., Hannay, T., Stratford, K. & Jack, J. Nature 360, 70–73 (1992).

    Article  ADS  CAS  Google Scholar 

  10. Stevens, C. F. & Wang, Y. Nature 371, 704–707 (1994).

    Article  ADS  CAS  Google Scholar 

  11. Mayer, M. L., Westbrook, G. L. & Guthrie, P. B. Nature 309, 261–263 (1984).

    Article  ADS  CAS  Google Scholar 

  12. Bekkers, J. M. & Stevens, C. F. Nature 341, 230–233 (1989).

    Article  ADS  CAS  Google Scholar 

  13. Muller, D., Joly, M. & Lynch, G. Science 242, 1694–1697 (1988).

    Article  ADS  CAS  Google Scholar 

  14. Kauer, J. A., Malenka, R. C. & Nicoll, R. A. Neuron 1, 911–917 (1988).

    Article  CAS  Google Scholar 

  15. Malgaroli, A. & Tsien, R. W. Nature 357, 134–139 (1992).

    Article  ADS  CAS  Google Scholar 

  16. Davies, S., Lester, R., Reyman, K. & Collingridge, G. Nature 330, 500–503 (1989).

    Article  ADS  Google Scholar 

  17. Aztely, F., Wigstrom, H. & Gustafsson, B. Eur. J. Neurosci. 4, 681–690 (1992).

    Article  Google Scholar 

  18. Maren, S., Tocco, G., Standley, S., Baudry, M. & Thompson, R. Proc. natn. Acad. Sci. U.S.A. 90, 9654–9658 (1993).

    Article  ADS  CAS  Google Scholar 

  19. McNaughton, B. L. J. Physiol., Lond. 324, 249–262 (1982).

    Article  CAS  Google Scholar 

  20. Wheeler, D. B., Randall, A. & Tsien, R. W. Science 264, 107–111 (1994).

    Article  ADS  CAS  Google Scholar 

  21. Wu, L. G. & Saggau, P. J. Neurosci. 14, 645–654 (1994).

    Article  CAS  Google Scholar 

  22. Manabe, T. & Nicoll, R. Science 265, 1888 (1994).

    Article  ADS  CAS  Google Scholar 

  23. Bashir, Z. I., Alford, S., Davies, S. N., Randall, A. D. & Collingridge, G. L. Nature 349, 156–158 (1991).

    Article  ADS  CAS  Google Scholar 

  24. Xie, X., Berger, T. W. & Barrionuevo, G. J. Neurophysiol. 67, 1009–1013 (1992).

    Article  CAS  Google Scholar 

  25. Tsien, R. W. & Malinow, R. Cold Spring Harb. Symp. quant. Biol. 55, 147–159 (1990).

    Article  CAS  Google Scholar 

  26. Dolphin, A., Errington, M. & Bliss, T. V. P. Nature 297, 496 (1982).

    Article  ADS  CAS  Google Scholar 

  27. Hessler, N. A., Shirke, A. M. & Malinow, R. Nature 366, 569–572 (1993).

    Article  ADS  CAS  Google Scholar 

  28. Hestrin, S., Sah, P. & Nicoll, R. Neuron 5, 247–253 (1990).

    Article  CAS  Google Scholar 

  29. Boulter, J. et al. Science 249, 1033–1037 (1990).

    Article  ADS  CAS  Google Scholar 

  30. Lynch, G. & Baudry, M. Science 224, 1057–1063 (1984).

    Article  ADS  CAS  Google Scholar 

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Liao, D., Hessler, N. & Malinow, R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400–404 (1995). https://doi.org/10.1038/375400a0

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