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. 1990 Sep;87(18):7165–7169. doi: 10.1073/pnas.87.18.7165

Failure to reverse long-term potentiation by coupling sustained presynaptic activity and N-methyl-D-aspartate receptor blockade.

R S Goldman 1, L E Chavez-Noriega 1, C F Stevens 1
PMCID: PMC54704  PMID: 1976253

Abstract

The proposal that long-term potentiation (LTP) is a mechanism underlying memory in the mammalian brain rests on a number of properties of LTP that parallel characteristics of memory defined by behavior. A prominent feature of behaviorally defined memory is its reversibility. LTP is induced at synapses that correlate in their activity, and the signal for induction is calcium influx through N-methyl-D-aspartate (NMDA) receptor channels. By analogy to the reversibility of behaviorially defined memory, uncorrelated synaptic activity might be expected to reverse LTP, an anti-Hebbian effect called long-term depression, which has only recently been described in the hippocampus [Stanton, P. K. & Sejnowski, T. J. (1989) Nature (London) 339, 215-218]. Because the extent to which synaptic activity is correlated is represented by postsynaptic calcium concentrations, it seemed likely to us that long-term depression is related to the failure of calcium to pass through the NMDA channel. One way to block the calcium influx that signals correlated synaptic activity is with the NMDA receptor antagonist D-(-)-2-amino-5-phosphonovalerate. We performed a series of experiments in rat hippocampal slices designed to estimate the amount of synaptic depression per afferent test pulse under these conditions. Schaffer collateral-commissural afferents to field CA1 were repetitively stimulated in the presence of 2-amino-5-phosphonovalerate. No enduring synaptic depression nor reversal of LTP could be detected. We conclude that some other mechanism underlies long-term depression in the hippocampus.

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Selected References

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  1. Abraham W. C., Goddard G. V. Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression. Nature. 1983 Oct 20;305(5936):717–719. doi: 10.1038/305717a0. [DOI] [PubMed] [Google Scholar]
  2. Andersen P., Sundberg S. H., Sveen O., Swann J. W., Wigström H. Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs. J Physiol. 1980 May;302:463–482. doi: 10.1113/jphysiol.1980.sp013256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blake J. F., Brown M. W., Collingridge G. L. CNQX blocks acidic amino acid induced depolarizations and synaptic components mediated by non-NMDA receptors in rat hippocampal slices. Neurosci Lett. 1988 Jun 29;89(2):182–186. doi: 10.1016/0304-3940(88)90378-3. [DOI] [PubMed] [Google Scholar]
  4. Bliss T. V., Gardner-Medwin A. R. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):357–374. doi: 10.1113/jphysiol.1973.sp010274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cline H. T., Debski E. A., Constantine-Paton M. N-methyl-D-aspartate receptor antagonist desegregates eye-specific stripes. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4342–4345. doi: 10.1073/pnas.84.12.4342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collingridge G. L., Kehl S. J., McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol. 1983 Jan;334:33–46. doi: 10.1113/jphysiol.1983.sp014478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crunelli V., Mayer M. L. Mg2+ dependence of membrane resistance increases evoked by NMDA in hippocampal neurones. Brain Res. 1984 Oct 8;311(2):392–396. doi: 10.1016/0006-8993(84)90107-0. [DOI] [PubMed] [Google Scholar]
  8. Davies S. N., Lester R. A., Reymann K. G., Collingridge G. L. Temporally distinct pre- and post-synaptic mechanisms maintain long-term potentiation. Nature. 1989 Apr 6;338(6215):500–503. doi: 10.1038/338500a0. [DOI] [PubMed] [Google Scholar]
  9. Errington M. L., Lynch M. A., Bliss T. V. Long-term potentiation in the dentate gyrus: induction and increased glutamate release are blocked by D(-)aminophosphonovalerate. Neuroscience. 1987 Jan;20(1):279–284. doi: 10.1016/0306-4522(87)90019-4. [DOI] [PubMed] [Google Scholar]
  10. Harris E. W., Ganong A. H., Cotman C. W. Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors. Brain Res. 1984 Dec 3;323(1):132–137. doi: 10.1016/0006-8993(84)90275-0. [DOI] [PubMed] [Google Scholar]
  11. Johnson J. W., Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987 Feb 5;325(6104):529–531. doi: 10.1038/325529a0. [DOI] [PubMed] [Google Scholar]
  12. Kleinschmidt A., Bear M. F., Singer W. Blockade of "NMDA" receptors disrupts experience-dependent plasticity of kitten striate cortex. Science. 1987 Oct 16;238(4825):355–358. doi: 10.1126/science.2443978. [DOI] [PubMed] [Google Scholar]
  13. Levy W. B., Steward O. Synapses as associative memory elements in the hippocampal formation. Brain Res. 1979 Oct 19;175(2):233–245. doi: 10.1016/0006-8993(79)91003-5. [DOI] [PubMed] [Google Scholar]
  14. Lynch G. S., Dunwiddie T., Gribkoff V. Heterosynaptic depression: a postsynaptic correlate of long-term potentiation. Nature. 1977 Apr 21;266(5604):737–739. doi: 10.1038/266737a0. [DOI] [PubMed] [Google Scholar]
  15. Lynch G., Larson J., Kelso S., Barrionuevo G., Schottler F. Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature. 1983 Oct 20;305(5936):719–721. doi: 10.1038/305719a0. [DOI] [PubMed] [Google Scholar]
  16. MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., Barker J. L. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. 1986 May 29-Jun 4Nature. 321(6069):519–522. doi: 10.1038/321519a0. [DOI] [PubMed] [Google Scholar]
  17. Malenka R. C., Kauer J. A., Zucker R. S., Nicoll R. A. Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission. Science. 1988 Oct 7;242(4875):81–84. doi: 10.1126/science.2845577. [DOI] [PubMed] [Google Scholar]
  18. Malinow R., Madison D. V., Tsien R. W. Persistent protein kinase activity underlying long-term potentiation. Nature. 1988 Oct 27;335(6193):820–824. doi: 10.1038/335820a0. [DOI] [PubMed] [Google Scholar]
  19. Mayer M. L., Westbrook G. L., Vyklický L., Jr Sites of antagonist action on N-methyl-D-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique. J Neurophysiol. 1988 Aug;60(2):645–663. doi: 10.1152/jn.1988.60.2.645. [DOI] [PubMed] [Google Scholar]
  20. Morris R. G. Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5. J Neurosci. 1989 Sep;9(9):3040–3057. doi: 10.1523/JNEUROSCI.09-09-03040.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  22. Stanton P. K., Sejnowski T. J. Associative long-term depression in the hippocampus induced by hebbian covariance. Nature. 1989 May 18;339(6221):215–218. doi: 10.1038/339215a0. [DOI] [PubMed] [Google Scholar]
  23. Wigström H., Gustafsson B., Huang Y. Y. Mode of action of excitatory amino acid receptor antagonists on hippocampal long-lasting potentiation. Neuroscience. 1986 Apr;17(4):1105–1115. doi: 10.1016/0306-4522(86)90080-1. [DOI] [PubMed] [Google Scholar]

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