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Presynaptic long-term depression at a central glutamatergic synapse: a role for CaMKII

Nature Neuroscience volume 1, pages 378–383 (1998)Cite this article

Abstract

CaMKII is a calcium-activated kinase that is abundant in neurons and has been strongly implicated in memory and learning. Here we show that low-frequency stimulation of glutamatergic afferents in hippocampal slices from juvenile domestic chicks results in long-term depression of synaptic transmission. This reduction does not require activation of NMDA or metabotropic glutamate receptors and does not require a rise in postsynaptic calcium. However, buffering presynaptic calcium prevents the reduction of the excitatory postsynaptic potential or current that is induced by low-frequency stimulation. In addition, application of the calmodulin antagonist calmidazolium, or the specific CaMKII antagonist KN-93, completely blocks long-term depression. These findings demonstrate a newly discovered form of long-term synaptic depression in the avian hippocampus.

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Figure 1: Low-frequency stimulation (LFS) induces long-term depression (LTD) of synaptic transmission.
Figure 2: NMDA-receptor activation is not required for LTD.
Figure 3: A rise in postsynaptic calcium is not required for LTD.
Figure 4: BAPTA buffers calcium in the dendritic tree.
Figure 5: Activation of metabotropic glutamate receptors is not required for LTD induction.
Figure 6: Induction of LTD requires a sustained rise in presynaptic calcium.
Figure 7: Induction of LTD requires activation of presynaptic calcium/calmodulin-dependent protein kinase II.

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Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia (J.R. and P.S.). P.S. is a Charles and Sylvia Viertel Senior Medical Research Fellow. T.M. was supported by an Australian Postgraduate Award.

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Author notes

  1. Pankaj Sah

    Present address: Division of Neuroscience, John Curtin School of Medical Research, GPO Box 334, ACT 2601, Australia

Authors and Affiliations

  1. The Neuroscience Group, Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, 2308, NSW, Australia

    Troy W. Margrie & John A. P. Rostas

  2. The Disciplines of Medical Biochemistry and Human Physiology, Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, 2308, NSW, Australia

    Pankaj Sah

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Correspondence to Pankaj Sah.

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Margrie, T., Rostas, J. & Sah, P. Presynaptic long-term depression at a central glutamatergic synapse: a role for CaMKII. Nat Neurosci 1, 378–383 (1998). https://doi.org/10.1038/1589

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