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. 1992 Jan 1;89(1):123–127. doi: 10.1073/pnas.89.1.123

Intracellular injection of Ca2+ chelators blocks induction of long-term depression in rat visual cortex.

S Bröcher 1, A Artola 1, W Singer 1
PMCID: PMC48188  PMID: 1309603

Abstract

In a variety of brain structures repetitive activation of synaptic connections can lead to long-term potentiation (LTP) or long-term depression (LTD) of synaptic transmission, and these modifications are held responsible for memory formation. Here we examine the role of postsynaptic Ca2+ concentration in the induction of LTD in the neocortex. In layer III cells of the rat visual cortex, LTD can be induced by tetanic stimulation of afferent fibers ascending from the white matter. We show that LTD induction is reliably blocked by intracellular injection of either EGTA or BAPTA [bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate], two different Ca2+ chelators. This confirms that the processes underlying the induction of LTD in neocortex are located postsynaptically and indicates that they depend on intracellular Ca2+ concentration. Thus, both LTP and LTD induction appear to involve calcium-mediated processes in the postsynaptic neuron. We propose that LTD is caused by a surge of calcium either through voltage-gated Ca2+ conductances and/or by transmitter-induced release of calcium from intracellular stores.

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Selected References

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  1. Adams P. R., Constanti A., Brown D. A., Clark R. B. Intracellular Ca2+ activates a fast voltage-sensitive K+ current in vertebrate sympathetic neurones. Nature. 1982 Apr 22;296(5859):746–749. doi: 10.1038/296746a0. [DOI] [PubMed] [Google Scholar]
  2. Alger B. E., Nicoll R. A. Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science. 1980 Dec 5;210(4474):1122–1124. doi: 10.1126/science.7444438. [DOI] [PubMed] [Google Scholar]
  3. Aniksztejn L., Ben-Ari Y. Novel form of long-term potentiation produced by a K+ channel blocker in the hippocampus. Nature. 1991 Jan 3;349(6304):67–69. doi: 10.1038/349067a0. [DOI] [PubMed] [Google Scholar]
  4. Artola A., Bröcher S., Singer W. Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex. Nature. 1990 Sep 6;347(6288):69–72. doi: 10.1038/347069a0. [DOI] [PubMed] [Google Scholar]
  5. Artola A., Singer W. Long-term potentiation and NMDA receptors in rat visual cortex. Nature. 1987 Dec 17;330(6149):649–652. doi: 10.1038/330649a0. [DOI] [PubMed] [Google Scholar]
  6. Artola A., Singer W. The Involvement of N-Methyl-D-Aspartate Receptors in Induction and Maintenance of Long-Term Potentiation in Rat Visual Cortex. Eur J Neurosci. 1990;2(3):254–269. doi: 10.1111/j.1460-9568.1990.tb00417.x. [DOI] [PubMed] [Google Scholar]
  7. Baranyi A., Szente M. B. Long-lasting potentiation of synaptic transmission requires postsynaptic modifications in the neocortex. Brain Res. 1987 Oct 13;423(1-2):378–384. doi: 10.1016/0006-8993(87)90867-5. [DOI] [PubMed] [Google Scholar]
  8. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  9. Bliss T. V., Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):331–356. doi: 10.1113/jphysiol.1973.sp010273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Crepel F., Jaillard D. Pairing of pre- and postsynaptic activities in cerebellar Purkinje cells induces long-term changes in synaptic efficacy in vitro. J Physiol. 1991 Jan;432:123–141. doi: 10.1113/jphysiol.1991.sp018380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eckert R., Chad J. E. Inactivation of Ca channels. Prog Biophys Mol Biol. 1984;44(3):215–267. doi: 10.1016/0079-6107(84)90009-9. [DOI] [PubMed] [Google Scholar]
  13. Grover L. M., Teyler T. J. Two components of long-term potentiation induced by different patterns of afferent activation. Nature. 1990 Oct 4;347(6292):477–479. doi: 10.1038/347477a0. [DOI] [PubMed] [Google Scholar]
  14. Hirsch J. C., Crepel F. Use-dependent changes in synaptic efficacy in rat prefrontal neurons in vitro. J Physiol. 1990 Aug;427:31–49. doi: 10.1113/jphysiol.1990.sp018159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ito M. Long-term depression. Annu Rev Neurosci. 1989;12:85–102. doi: 10.1146/annurev.ne.12.030189.000505. [DOI] [PubMed] [Google Scholar]
  16. Kimura F., Tsumoto T., Nishigori A., Yoshimura Y. Long-term depression but not potentiation is induced in Ca(2+)-chelated visual cortex neurons. Neuroreport. 1990 Sep;1(1):65–68. doi: 10.1097/00001756-199009000-00018. [DOI] [PubMed] [Google Scholar]
  17. Linden D. J., Dickinson M. H., Smeyne M., Connor J. A. A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons. Neuron. 1991 Jul;7(1):81–89. doi: 10.1016/0896-6273(91)90076-c. [DOI] [PubMed] [Google Scholar]
  18. Lisman J. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9574–9578. doi: 10.1073/pnas.86.23.9574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. McCormick D. A., Connors B. W., Lighthall J. W., Prince D. A. Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J Neurophysiol. 1985 Oct;54(4):782–806. doi: 10.1152/jn.1985.54.4.782. [DOI] [PubMed] [Google Scholar]
  22. Sakurai M. Calcium is an intracellular mediator of the climbing fiber in induction of cerebellar long-term depression. Proc Natl Acad Sci U S A. 1990 May;87(9):3383–3385. doi: 10.1073/pnas.87.9.3383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schwartzkroin P. A., Stafstrom C. E. Effects of EGTA on the calcium-activated afterhyperpolarization in hippocampal CA3 pyramidal cells. Science. 1980 Dec 5;210(4474):1125–1126. doi: 10.1126/science.6777871. [DOI] [PubMed] [Google Scholar]
  24. Schwindt P. C., Spain W. J., Foehring R. C., Chubb M. C., Crill W. E. Slow conductances in neurons from cat sensorimotor cortex in vitro and their role in slow excitability changes. J Neurophysiol. 1988 Feb;59(2):450–467. doi: 10.1152/jn.1988.59.2.450. [DOI] [PubMed] [Google Scholar]
  25. Schwindt P. C., Spain W. J., Foehring R. C., Stafstrom C. E., Chubb M. C., Crill W. E. Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro. J Neurophysiol. 1988 Feb;59(2):424–449. doi: 10.1152/jn.1988.59.2.424. [DOI] [PubMed] [Google Scholar]
  26. Sladeczek F., Pin J. P., Récasens M., Bockaert J., Weiss S. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature. 1985 Oct 24;317(6039):717–719. doi: 10.1038/317717a0. [DOI] [PubMed] [Google Scholar]
  27. Stanton P. K., Chattarji S., Sejnowski T. J. 2-Amino-3-phosphonopropionic acid, an inhibitor of glutamate-stimulated phosphoinositide turnover, blocks induction of homosynaptic long-term depression, but not potentiation, in rat hippocampus. Neurosci Lett. 1991 Jun 10;127(1):61–66. doi: 10.1016/0304-3940(91)90895-z. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Sugimori M., Llinás R. R. Real-time imaging of calcium influx in mammalian cerebellar Purkinje cells in vitro. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5084–5088. doi: 10.1073/pnas.87.13.5084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tsien R. W., Lipscombe D., Madison D. V., Bley K. R., Fox A. P. Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci. 1988 Oct;11(10):431–438. doi: 10.1016/0166-2236(88)90194-4. [DOI] [PubMed] [Google Scholar]
  31. Yoshimura Y., Tsumoto T., Nishigori A. Input-specific induction of long-term depression in Ca(2+)-chelated visual cortex neurons. Neuroreport. 1991 Jul;2(7):393–396. doi: 10.1097/00001756-199107000-00010. [DOI] [PubMed] [Google Scholar]

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