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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jun;87(11):4073–4077. doi: 10.1073/pnas.87.11.4073

Protein kinase C activity is not responsible for the expression of long-term potentiation in hippocampus.

D Muller 1, P A Buchs 1, Y Dunant 1, G Lynch 1
PMCID: PMC54049  PMID: 2161529

Abstract

Long-term potentiation (LTP) in hippocampus has been proposed to result from a tonic activation of protein kinase C. This hypothesis predicts that stimulation of the kinase would produce a smaller change in response size on potentiated versus control pathways and, conversely, that inhibition of the kinase would reduce potentiated inputs to a greater degree than control responses. We tested these predictions using phorbol esters to activate and using the antagonist H-7 to inhibit protein kinase C; we found that the actions of these drugs on synaptic transmission were not affected by prior induction of LTP. Both compounds, however, significantly decreased the contribution of N-methyl-D-aspartate receptors to synaptic potentials, a result that accounts for the suppressive effects of these compounds on LTP formation. Thus protein kinase C is probably not involved in the expression of LTP but may play a role in the receptor-mediated events participating in its induction.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akers R. F., Lovinger D. M., Colley P. A., Linden D. J., Routtenberg A. Translocation of protein kinase C activity may mediate hippocampal long-term potentiation. Science. 1986 Feb 7;231(4738):587–589. doi: 10.1126/science.3003904. [DOI] [PubMed] [Google Scholar]
  2. Alkon D. L., Rasmussen H. A spatial-temporal model of cell activation. Science. 1988 Feb 26;239(4843):998–1005. doi: 10.1126/science.2830669. [DOI] [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. Dunwiddie T., Lynch G. Long-term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency. J Physiol. 1978 Mar;276:353–367. doi: 10.1113/jphysiol.1978.sp012239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gustafsson B., Huang Y. Y., Wigström H. Phorbol ester-induced synaptic potentiation differs from long-term potentiation in the guinea pig hippocampus in vitro. Neurosci Lett. 1988 Feb 15;85(1):77–81. doi: 10.1016/0304-3940(88)90432-6. [DOI] [PubMed] [Google Scholar]
  7. Kauer J. A., Malenka R. C., Nicoll R. A. A persistent postsynaptic modification mediates long-term potentiation in the hippocampus. Neuron. 1988 Dec;1(10):911–917. doi: 10.1016/0896-6273(88)90148-1. [DOI] [PubMed] [Google Scholar]
  8. Larson J., Lynch G. Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events. Science. 1986 May 23;232(4753):985–988. doi: 10.1126/science.3704635. [DOI] [PubMed] [Google Scholar]
  9. Larson J., Wong D., Lynch G. Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res. 1986 Mar 19;368(2):347–350. doi: 10.1016/0006-8993(86)90579-2. [DOI] [PubMed] [Google Scholar]
  10. Lovinger D. M., Wong K. L., Murakami K., Routtenberg A. Protein kinase C inhibitors eliminate hippocampal long-term potentiation. Brain Res. 1987 Dec 8;436(1):177–183. doi: 10.1016/0006-8993(87)91573-3. [DOI] [PubMed] [Google Scholar]
  11. MacDonald J. F., Mody I., Salter M. W. Regulation of N-methyl-D-aspartate receptors revealed by intracellular dialysis of murine neurones in culture. J Physiol. 1989 Jul;414:17–34. doi: 10.1113/jphysiol.1989.sp017674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Malenka R. C., Ayoub G. S., Nicoll R. A. Phorbol esters enhance transmitter release in rat hippocampal slices. Brain Res. 1987 Feb 10;403(1):198–203. doi: 10.1016/0006-8993(87)90145-4. [DOI] [PubMed] [Google Scholar]
  13. Malenka R. C., Madison D. V., Nicoll R. A. Potentiation of synaptic transmission in the hippocampus by phorbol esters. Nature. 1986 May 8;321(6066):175–177. doi: 10.1038/321175a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Malinow R., Schulman H., Tsien R. W. Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. Science. 1989 Aug 25;245(4920):862–866. doi: 10.1126/science.2549638. [DOI] [PubMed] [Google Scholar]
  16. Muller D., Joly M., Lynch G. Contributions of quisqualate and NMDA receptors to the induction and expression of LTP. Science. 1988 Dec 23;242(4886):1694–1697. doi: 10.1126/science.2904701. [DOI] [PubMed] [Google Scholar]
  17. Muller D., Lynch G. Long-term potentiation differentially affects two components of synaptic responses in hippocampus. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9346–9350. doi: 10.1073/pnas.85.23.9346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Muller D., Lynch G. N-methyl-D-aspartate receptor-mediated component of synaptic responses to single-pulse stimulation in rat hippocampal slices. Synapse. 1988;2(6):666–668. doi: 10.1002/syn.890020614. [DOI] [PubMed] [Google Scholar]
  19. Muller D., Turnbull J., Baudry M., Lynch G. Phorbol ester-induced synaptic facilitation is different than long-term potentiation. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6997–7000. doi: 10.1073/pnas.85.18.6997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shapira R., Silberberg S. D., Ginsburg S., Rahamimoff R. Activation of protein kinase C augments evoked transmitter release. Nature. 1987 Jan 1;325(6099):58–60. doi: 10.1038/325058a0. [DOI] [PubMed] [Google Scholar]

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