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Plasticity of calcium channels in dendritic spines

Nature Neuroscience volume 6, pages 948–955 (2003)Cite this article

Abstract

Voltage-sensitive Ca2+ channels (VSCCs) constitute a major source of calcium ions in dendritic spines, but their function is unknown. Here we show that R-type VSCCs in spines of rat CA1 pyramidal neurons are depressed for at least 30 min after brief trains of back-propagating action potentials. Populations of channels in single spines are depressed stochastically and synchronously, independent of channels in the parent dendrite and other spines, implying that depression is the result of signaling restricted to individual spines. Induction of VSCC depression blocks theta-burst-induced long-term potentiation (LTP), indicating that postsynaptic action potentials can modulate synaptic plasticity by tuning VSCCs. Induction of depression requires [Ca2+] elevations and activation of L-type VSCCs, which activate Ca2+/calmodulin-dependent kinase II (CaMKII) and a cyclic adenosine monophosphate (cAMP)-dependent pathway. Given that L-type VSCCs do not contribute measurably to Ca2+ influx in spines, they must activate downstream effectors either directly through voltage-dependent conformational changes or via [Ca2+] microdomains.

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Figure 1: Activity-dependent depression of action potential-evoked [Ca2+] transients in spines.
Figure 2: Types of calcium channels in spines and dendrites.
Figure 3: Depression is due to a change in the probability of opening in response to an action potential.
Figure 4: All-or-none depression of [Ca2+] transients (Δ[Ca2+]AP).
Figure 5: Depression of VSCCs interferes with induction of LTP.
Figure 6: Mechanism of activity-dependent depression of VSCCs.

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Acknowledgements

The authors thank T. Soderling for CaMKII*, T. Oertner, P. O'Brien and B. Burbach for help with experiments, and G. Buzsaki, A. Ghosh, R. Iyengar, R. Malinow and members of our laboratory for a critical reading of the manuscript. This work was supported by the Japan Society for the Promotion of Science (to R.Y.), the Burroughs Wellcome Fund (to R.Y. and B.S.), the Mathers and Pew Foundations, and the US National Institutes of Health (NIH).

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  1. Bernardo L Sabatini

    Present address: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts, 02115, USA

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  1. Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, 11724, New York, USA

    Ryohei Yasuda, Bernardo L Sabatini & Karel Svoboda

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Supplementary information

Supplementary Fig. 1.

Relationship between calcium influx in response to a single action potential and spine volume. Spine volume was measured as in ref. 24. (PDF 191 kb)

Supplementary Fig. 2.

Schematic showing the signal transduction pathway causing DCC (see text for details). Red arrows, Ca2+ influx; black arrows, intracellular pathways. Dashed lines indicated putative interactions. (PDF 218 kb)

Supplementary Note (PDF 19 kb)

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Yasuda, R., Sabatini, B. & Svoboda, K. Plasticity of calcium channels in dendritic spines. Nat Neurosci 6, 948–955 (2003). https://doi.org/10.1038/nn1112

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