Postsynaptic Mechanisms Involved in Long-Term Potentiation

  • Julie A. Kauer
  • Robert C. Malenka
  • David J. Perkel
  • Roger A. Nicoll
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 268)


Long-term potentiation (LTP) is a persistent enhancement of synaptic transmission observed at excitatory synapses in the mammalian hippocampus (Bliss and Lomo, 1973). This phenomenon is one of the most striking examples of synaptic plasticity in the vertebrate brain, and has been intensively studied as a model for learning and memory. LTP can be divided into two parts, the triggering or initiation events, and the long-lasting alteration in synaptic strength. In the past six years a considerable body of work has clarified some of the processes involved in triggering LTP, and it has become widely accepted that these processes are localized to the postsynaptic neuron. In contrast, the processes responsible for maintaining the potentiation over time are not as clearly understood, and the synaptic site of these processes remains controversial. This chapter will focus on work from our laboratory studying the cellular mechanisms involved in LTP at the Schaffer collateral-pyramidal cell synapse in the CA1 region of the hippocampal slice preparation.


Synaptic Transmission Postsynaptic Neuron Postsynaptic Cell NMDA Channel NMDA Component 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akers, R. E., Lovinger, D. M., Colley, P. A., Linden, D. J. and Routtenberg, A., 1986, Translocation of protein kinase C activity may mediate hippocampal long-term potentiation, Science 231: 587.PubMedCrossRefGoogle Scholar
  2. Ascher, P. and Nowak, L., 1988, The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture, J. Physiol 399: 247.PubMedGoogle Scholar
  3. Bliss, T. V. P. and Lemo, T., 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path, J. Physiol 232: 331.PubMedGoogle Scholar
  4. Bliss, T. V. P., Douglas, R. M., Errington, M. L., and Lynch, M. A., 1986, Correlation between long-term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats, J. Physiol 377: 391.PubMedGoogle Scholar
  5. Chang, F.-F., and Greenough, W. T., 1984, Transient and enduring morphological correlates of synaptic activity and efficacy change in the rat hippocampal slice, Brain Res. 309: 35.PubMedCrossRefGoogle Scholar
  6. Coan, E. J. and Collingridge, G. L., 1985, Magnesium ions block an N-methyl-D-aspartate receptor-mediated component of synaptic transmission in rat hippocampus, Neurosci. Lett 53: 21.PubMedCrossRefGoogle Scholar
  7. Collingridge, G. L., Kehl, S. J. and McLennan, H., 1983, Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus, J. Physiol 334: 33.PubMedGoogle Scholar
  8. Forsythe, I. D. and Westbrook, G. L., 1988, Slow excitatory postsynaptic currents mediated by N-methyl-D-aspartate receptors on mouse cultured central neurones, J. Physiol 396: 515.PubMedGoogle Scholar
  9. Gustafsson, B., Wigström, H., Abraham,W. C. and Huang, Y.-Y., 1987, Long-term potentiation in the hippocampus using depolarizing current pulses as the conditioning stimulus to single volley synaptic potentials, J. Neurosci 7: 774.Google Scholar
  10. Hu, G. -Y., Hvalby, O., Walaas, S.I., Albert, K. A., Skjeflo, P., Andersen, P., and Greengard, P., 1987, Protein kinase C injection into hippocampal pyramidal cells elicits features of long term potentiation, Nature, 328: 426.PubMedCrossRefGoogle Scholar
  11. Jahr, C. E. and Stevens, C. F., 1987, Glutamate activates multiple single channel conductances in hippocampal neurones, Nature 325: 522.PubMedCrossRefGoogle Scholar
  12. Kauer, J. A., Malenka, R. C. and Nicoll, R. A., 1988a, A persistent postsynaptic modification mediates long-term potentiation in the hippocampus, Neuron 1: 911.PubMedCrossRefGoogle Scholar
  13. Kauer, J. A., Malenka, R. C. and Nicoll, R. A., 1988b, NMDA application potentiates synaptic transmission in the hippocampus, Nature 334: 250.PubMedCrossRefGoogle Scholar
  14. Kelly, P. T., McGuinness, T. L., and Greengard, P., 1984, Evidence that the major postsynaptic density protein is a component of a Cat+/calmodulin-dependent protein kinase, Proc. Natl. Acad. Sci. USA 81: 945.PubMedCrossRefGoogle Scholar
  15. Kelly, P. T., Weinberger, R. P., and Waxham, M. N., 1988, Active site-directed inhibition of Cat+ /calmodulin-dependent protein kinase type II by a bifunctional calmodulin-binding peptide, Proc. Natl. Acad. Sci USA 85: 4991.PubMedCrossRefGoogle Scholar
  16. Kelso, S. R., Ganong, A. H. and Brown, T. H., 1986, Hebbian synapses in hippocampus, Proc. Natl. Acad. Sci. USA 83: 5326.PubMedCrossRefGoogle Scholar
  17. Kennedy, M. B., Bennett, M. K., and Erondu, N. E., 1983, Biochemical and immunochemical evidence that the “major postsynaptic density protein” is a subunit of a calmodulin-dependent protein kinase, Proc. Natl. Acad. Sci. USA 80: 7357.PubMedCrossRefGoogle Scholar
  18. Lee, K. S. Schottler, F., Oliver, M., and Lynch, G., 1980, Brief bursts of high-frequency stimulation produce two types of structural change in rat hippocampus, J. Neurophysiol 44: 247.Google Scholar
  19. Lovinger, D. M., Wong, K. L., Murakami, K. and Routtenberg, A., 1987, Protein kinase C inhibitors eliminate hippocampal long-term potentiation, Brain Res. 436: 177.PubMedCrossRefGoogle Scholar
  20. Lynch, G. and Baudry, M., 1984, The biochemistry of memory: a new and specifichypothesis, Science 224: 1057.PubMedCrossRefGoogle Scholar
  21. Lynch, G., J. Larson, S. Kelso, G. Barrioneuevo and F. Schottler, 1983, Intracellular injections of EGTA block induction of hippocampal long-term potentiation, Nature 305: 719.PubMedCrossRefGoogle Scholar
  22. Lynch, M. A., Clements, M., Errington, M. L., and Bliss, T. V. P., 1988, Increased hydrolysis of phosphatidylinositol-4,5-bisphosphate in long-term potentiation, Neurosci. Lett 84: 291.PubMedCrossRefGoogle Scholar
  23. MacDermott, A. B., Mayer, M. L., Westbrook, G.L., Smith, S. J. and Barker. J. L., 1986, NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones, Nature 321: 519.PubMedCrossRefGoogle Scholar
  24. Malenka, R. C., Kauer, J. A., Zucker, R. S. and Nicoll, R. A., 1988, Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission, Science 242: 81.PubMedCrossRefGoogle Scholar
  25. Malenka, R. C., Kauer, J. A., Zucker, R. S. and Nicoll, R. A., 1988, Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission, Science 242: 81.PubMedCrossRefGoogle Scholar
  26. Malenka, R. C., Kauer, J. A., Zucker, R. S. and Nicoll, R. A., 1988, Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission, Science 242: 81.PubMedCrossRefGoogle Scholar
  27. Malinow, R., Madison, D. V. and Tsien, R. W., 1988, Persistent protein kinase activity underlying long-term potentiation, Nature 335: 820PubMedCrossRefGoogle Scholar
  28. Mayer, M. L., Westbrook, G. L. and Guthrie, P. B., 1984, Voltage-dependent block by Mgt+ of NMDA responses in spinal cord neurones, Nature 309: 262.CrossRefGoogle Scholar
  29. Mayer, M. L., MacDermott, A. B., Westbrook, G. L., Smith, S. J. and Barker, J. L., 1987, Agonistand voltage-gated calcium entry in cultured mouse spinal cord neurons under voltage clamp, J. Neurosci 7: 3230.PubMedGoogle Scholar
  30. Mayer, M. L. and Westbrook, G. L., 1987, Permeation and block of N-methyl-D-aspartatic acid receptor channels by divalent cations in mouse central neurones, J. Physiol 394: 501.PubMedGoogle Scholar
  31. Miller, S. G. and Kennedy, M. B., 1986, Regulation of brain type II Cat+/calmodulin-dependent protein kinase by autophosphorylation: a Ca2+-triggered molecular switch, Cell 44: 861.PubMedCrossRefGoogle Scholar
  32. Muller, D. and Lynch, G., 1988, Long-term potentiation differentially affects two components of synaptic responses in hippocampus, Proc. Natl. Acad. Sci. USA 85: 9346.PubMedCrossRefGoogle Scholar
  33. Muller, D., Joly, M., and Lynch, G., 1988, Contributions of quisqualate and NMDA receptors to the induction and expression of LTP, Science, 242: 1694–1697.PubMedCrossRefGoogle Scholar
  34. Nelson, R. B., and Routtenberg, A., 1985, Characterization of protein Fl (47kDa, 4.5 pI): a kinase C substrate directly related to neural plasticity, Exp. Neurol 89: 213.PubMedCrossRefGoogle Scholar
  35. Nowak, L., Bregestovski, P.,Ascher, P., Herbet, A., and Prochiantz, A., 1984, Magnesium gates glutamate-activated channels in mouse central neurones, Nature 307: 462.PubMedCrossRefGoogle Scholar
  36. Ouimet, C. C., McGuinness, T. L. and Greengard, P., Immunocytochemical localization of calcium/calmodulin-dependent protein kinase II in rat brain, Proc. Natl. Acad. Sci. USA 81: 5604.Google Scholar
  37. Reymann, K. G., Frey, U., Jork, R. and Matthies, H., 1988, Polymixin B, an inhibitor of protien kinase C, prevents the maintenance of synaptic long—term potentiation in hippocampal CAl neurons, Brain Res. 440: 305.PubMedCrossRefGoogle Scholar
  38. Saitoh, T. and Schwartz, J. H., 1985, Phosphorylation-dependent subcellular translocation of a Cat+ /calmodulin-dependent protein kinase produces an autonomous enzyme in Aplysia neurons, J. Cell Biol 100: 835.PubMedCrossRefGoogle Scholar
  39. Sastry, B. R., Goh, J. W. and Auyeung, A., 1986, Associative induction of posttetanic and long-term potentiation in CAl neurons of rat hippocampus, Science 232: 988.PubMedCrossRefGoogle Scholar
  40. Staubli, U., Larson, J., Thibault, O., Baudry, M., and Lynch, G., 1988, Chronic administration of a thiol-proteinase inhibitor blocks long-term potentiation of synaptic responses, Brain Res. 444: 153.PubMedCrossRefGoogle Scholar
  41. Wigstrom, H. and Gustafsson, B., 1988, Presynaptic and postsynaptic interactions in the control of hippocampal long-term potentiation, in: “Long-term Potentiation: From Biophysics to Behavior”. Landfield and Deadwyler ed., Alan R. Liss, Inc., New York.Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Julie A. Kauer
    • 1
  • Robert C. Malenka
    • 1
  • David J. Perkel
    • 1
  • Roger A. Nicoll
    • 1
  1. 1.Departments of Pharmacology and PhysiologyUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations