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Calcium stores regulate the polarity and input specificity of synaptic modification

Nature volume 408, pages 584–588 (2000)Cite this article

Abstract

Activity-induced synaptic modification is essential for the development and plasticity of the nervous system1,2,3. Repetitive correlated activation of pre- and postsynaptic neurons can induce persistent enhancement or decrement of synaptic efficacy, commonly referred to as long-term potentiation or depression2,3(LTP or LTD). An important unresolved issue is whether and to what extent LTP and LTD are restricted to the activated synapses4,5,6,7,8. Here we show that, in the CA1 region of the hippocampus, reduction of postsynaptic calcium influx by partial blockade of NMDA (N-methyl-d-aspartate) receptors results in a conversion of LTP to LTD and a loss of input specificity normally associated with LTP, with LTD appearing at heterosynaptic inputs. The induction of LTD at homo- and heterosynaptic sites requires functional ryanodine receptors and inositol triphosphate (InsP3) receptors, respectively. Functional blockade or genetic deletion of type 1 InsP3 receptors led to a conversion of LTD to LTP and elimination of heterosynaptic LTD, whereas blocking ryanodine receptors eliminated only homosynaptic LTD. Thus, postsynaptic Ca2+, deriving from Ca2+ influx and differential release of Ca2+ from internal stores through ryanodine and InsP3 receptors, regulates both the polarity and input specificity of activity-induced synaptic modification.

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Figure 1: LTP/LTD induced by correlated pre- and postsynaptic activity in hippocampal CA1 pyramidal neurons.
Figure 2: Critical time windows for the induction of LTP/LTD by correlated pre- and postsynaptic activation.
Figure 3: Effects of partial blockade of NMDA receptors.
Figure 4: Effects of blocking Ca2+ release from internal stores on the induction of LTD.
Figure 5: Effects of blocking internal Ca2+ release on the induction of LTP.
Figure 6: A model for the roles of postsynaptic Ca2+ signalling in synaptic modification.

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References

  1. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133– 1138 (1996).

    Article  ADS  CAS  Google Scholar 

  2. Bliss, T. V. P. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 ( 1993).

    Article  ADS  CAS  Google Scholar 

  3. Martin, S. J., Grimwood, P. D. & Morris, R. G. M. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000).

    Article  CAS  Google Scholar 

  4. Schuman, E. M. & Madison, D. V. Locally distributed synaptic potentiation in the hippocampus. Science 263, 532–536 (1994).

    Article  ADS  CAS  Google Scholar 

  5. Staubli, U. V. & Ji, Z.-X. The induction of homo- vs. heterosynaptic LTD in area CA1 of hippocampal slices from adult rats. Brain Res. 714, 169–176 ( 1996).

    Article  CAS  Google Scholar 

  6. Engert, F. & Bonhoeffer, T. Synapse specificity of long-term potentiation breaks down at short distances. Nature 388, 279–284 (1997).

    Article  ADS  CAS  Google Scholar 

  7. Fitzsimonds, R. M., Song, H.-j. & Poo, M.-m. Propagation of activity-dependent synaptic depression in simple neural networks. Nature 388, 439 –448 (1997).

    Article  ADS  CAS  Google Scholar 

  8. Tao, H.-z., Zhang, L. I., Bi, G.-q. & Poo, M.-m. Selective presynaptic propagation of long-term potentiation in defined neural networks. J. Neurosci. 20, 3233–3243 (2000).

    Article  CAS  Google Scholar 

  9. Lisman, J. E. Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate–CA3 interactions. Neuron 22 , 233–242 (1999).

    Article  CAS  Google Scholar 

  10. Zhang, L. I. et al. A critical window for cooperation and competition among developing retinotectal synapses. Nature 395, 37– 44 (1998).

    Article  ADS  CAS  Google Scholar 

  11. Bi, G.-q. & Poo, M.-m. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J. Neurosci. 18, 10464– 10472 (1998).

    Article  CAS  Google Scholar 

  12. Cummings, J. A., Mulkey, R. M., Nicoll, R. A. & Malenka, R. C. Ca2+ signaling requirements for long-term depression in the hippocampus. Neuron 16, 825– 833 (1996).

    Article  CAS  Google Scholar 

  13. Bienenstock, E. L., Cooper, L. N. & Munro, P. W. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J. Neurosci. 2, 32–48 ( 1982).

    Article  CAS  Google Scholar 

  14. Artola, A. & Singer, W. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends Neurosci. 16, 480–487 (1993).

    Article  CAS  Google Scholar 

  15. Bear, M. Mechanism for a sliding synaptic modification threshold. Neuron 15, 1–4 (1995 ).

    Article  CAS  Google Scholar 

  16. Emptage, N., Bliss, T. V. P. & Fine, A. single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines. Neuron 22, 115–124 ( 1999).

    Article  CAS  Google Scholar 

  17. Berridge, M. J. Neuronal calcium signaling. Neuron 21, 13 –26 (1998).

    Article  CAS  Google Scholar 

  18. Furuichi, T., Kohda, K., Miyawaki, A. & Mikoshiba, K. Intracellular channels. Curr. Opin. Neurobiol. 4, 294– 303 (1994).

    Article  CAS  Google Scholar 

  19. Matsumoto, M. et al. Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor. Nature 379, 168–171 (1996).

    Article  ADS  CAS  Google Scholar 

  20. Oliet, S. H. R., Malenka, R. C. & Nicoll, R. A. Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells. Neuron 18, 969–982 (1997).

    Article  CAS  Google Scholar 

  21. Pin, J.-P. & Duvoisin, R. Neurotransmitter receptors. I. The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34, 1–26 (1995).

    Article  CAS  Google Scholar 

  22. Conner, J. A. & Stevens, C. F. Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma. J. Physiol. 213, 31–53 ( 1971).

    Article  Google Scholar 

  23. Cordoba-Rodriguez, R., Moore, K. Y., Kao, J. P. Y. & Weinreich, D. Calcium regulation of a slow post-spike hyperpolarization in vagal afferent neurons. Proc. Natl Acad. Sci. USA 96, 7650 –7657 (1999).

    Article  ADS  CAS  Google Scholar 

  24. Futatsugi, A. et al. Facilitation of NMDA-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3. Neuron 24, 701–713 (1999).

    Article  CAS  Google Scholar 

  25. Fagni, L., Chavis, P., Ango F. & Bockaert, J. Complex interactions between mGluRs, intracellular Ca2+ stores and ion channels in neurons. Trends Neurosci. 23, 80–88 (2000).

    Article  CAS  Google Scholar 

  26. Bezprozvanny, I., Watras, J. & Ehrlich, B. E. Bell-shaped calcium-response curves of Ins(1,4,5)P 3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature 351, 751–754 (1991).

    Article  ADS  CAS  Google Scholar 

  27. Lisman, J. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc. Natl Acad. Sci. USA 86, 9574 –9578 (1989).

    Article  ADS  CAS  Google Scholar 

  28. Yang, S.-N., Tang, Y.-G. & Zucker, R. S. Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. J. Neurophysiol. 81, 781–787 ( 1999).

    Article  CAS  Google Scholar 

  29. Nakamura, T., Barbara, J.-G., Nakamura, K. & Ross, W. N. Synergistic release of Ca2+ from InsP3-sensitive stores evoked by synaptic activation of mGluRs paired with backpropagating action potentials. Neuron 24, 727– 737 (1999).

    Article  CAS  Google Scholar 

  30. Kato, K., Clifford, D. B. & Zorumski, C. F. Long-term potentiation during whole-cell recording in rat hippocampal slices. Neuroscience 53, 39–47 (1993).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank T. Michikawa for providing an antibody against InsP3R1; T. V. P. Bliss and R. C. Malenka for helpful discussions and suggestions; and N. Spitzer, J. R. Henley, D. Zacharias, A. F. Schinder, S. Andersen and F. Engert for critical comments on the manuscript. This work was supported in part by a grant from USNIH.

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Author notes

  1. Makoto Nishiyama & Kyonsoo Hong

    Present address: Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, New York, 10016, USA

  2. Mu-ming Poo

    Present address: Department of Molecular and Cell Biology, University of California, Berkeley, California, 94720, USA

  3. Makoto Nishiyama and Kunio Kato: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, University of California at San Diego, La Jolla, 92093-0357, California, USA

    Makoto Nishiyama, Kyonsoo Hong & Mu-ming Poo

  2. Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST), Tokyo, 113-0021, Japan

    Katsuhiko Mikoshiba, Mu-ming Poo & Kunio Kato

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Correspondence to Mu-ming Poo.

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Nishiyama, M., Hong, K., Mikoshiba, K. et al. Calcium stores regulate the polarity and input specificity of synaptic modification. Nature 408, 584–588 (2000). https://doi.org/10.1038/35046067

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