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AMPA receptor–PDZ interactions in facilitation of spinal sensory synapses

Nature Neuroscience volume 2, pages 972–977 (1999)Cite this article

Abstract

Silent synapses form between some primary sensory afferents and dorsal horn neurons in the spinal cord. Molecular mechanisms for activation or conversion of silent synapses to conducting synapses are unknown. Serotonin can trigger activation of silent synapses in dorsal horn neurons by recruiting AMPA receptors. AMPA-receptor subunits GluR2 and GluR3 interact via their cytoplasmic C termini with PDZ-domain-containing proteins such as GRIP (glutamate receptor interacting protein), but the functional significance of these interactions is unclear. Here we demonstrate that protein interactions involving the GluR2/3 C terminus are important for serotonin-induced activation of silent synapses in the spinal cord. Furthermore, PKC is a necessary and sufficient trigger for this activation. These results implicate AMPA receptor–PDZ interactions in mechanisms underlying sensory synaptic potentiation and provide insights into the pathogenesis of chronic pain.

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Figure 1: Expression of GluR2/3 and GRIP in spinal cord dorsal horn neurons.
Figure 2: GluR2-SVKI and GluR2-SVKE peptides do not affect baseline AMPA receptor-mediated responses in spinal cord dorsal horn neurons.
Figure 3: GluR2-SVKI selectively blocks synaptic facilitation induced by 5-HT.
Figure 4: Postsynaptic PKC activation is necessary and sufficient for synaptic facilitation by 5-HT.
Figure 5: GluR2-SVKI inhibits the activation of silent glutamatergic synapses.

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Acknowledgements

This work was supported in part by grants from the NIH (NIDA, NINDS, M.Z.; NINDS, J.E.H.; NINDS, M.S.). M.S. is Assistant Investigator of the Howard Hughes Medical Institute. C.S. is a Fellow of the Armenise-Harvard Foundation.

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Authors and Affiliations

  1. Department of Anesthesiology, Anatomy & Neurobiology, Washington University School of Medicine, Campus Box 8054, 660S. Euclid Avenue, St. Louis, 63110, Missouri, USA

    Ping Li, Geoffrey A. Kerchner, Feng Wei & Min Zhuo

  2. Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, Massachusetts, USA

    Carlo Sala & Morgan Sheng

  3. Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, 63110, Missouri, USA

    James E. Huettner

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  1. Ping Li
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Correspondence to Min Zhuo.

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Li, P., Kerchner, G., Sala, C. et al. AMPA receptor–PDZ interactions in facilitation of spinal sensory synapses. Nat Neurosci 2, 972–977 (1999). https://doi.org/10.1038/14771

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