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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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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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