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Internalization of ionotropic glutamate receptors in response to mGluR activation

Nature Neuroscience volume 4, pages 1079–1085 (2001)Cite this article

Abstract

Activation of group 1 metabotropic glutamate receptors (mGluRs) stimulates dendritic protein synthesis and long-term synaptic depression (LTD), but it remains unclear how these effects are related. Here we provide evidence that a consequence of mGluR activation in the hippocampus is the rapid loss of both AMPA and NMDA receptors from synapses. Like mGluR-LTD, the stable expression of this change requires protein synthesis. These data suggest that expression of mGluR-LTD is at least partly postsynaptic, and that a functional consequence of dendritic protein synthesis is the regulation of glutamate receptor trafficking.

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Figure 1: mGluR stimulation induces endocytosis of GluR1 puncta.
Figure 2: mGluR stimulation induces loss of synaptic surface AMPARs.
Figure 3: mGluR stimulation induces loss of surface GluR1.
Figure 4: DHPG-induced synaptic depression is accompanied by a reduction in AMPAR-mediated mEPSC frequency.
Figure 5: mGluR stimulation induces loss of synaptic surface NMDARs.
Figure 6: DHPG application attenuates synaptically evoked NMDAR-mediated EPSCs and NMDA-evoked currents.

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Acknowledgements

We thank P. Ornstein at Eli Lilly for the LY344545, S. Won, M. Milekic and E. Glater for assistance, and M. Colledge and H.-K. Lee for advice. This work was supported in part by NIH Grant #NS39321.

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Authors and Affiliations

  1. Department of Neuroscience, Brown University, Providence, 02912, Rhode Island, USA

    Eric M. Snyder, Benjamin D. Philpot, Kimberly M. Huber, Xin Dong, Justin R. Fallon & Mark F. Bear

  2. Howard Hughes Medical Institute, Brown University, Providence, 02912, Rhode Island, USA

    Eric M. Snyder, Benjamin D. Philpot, Kimberly M. Huber & Mark F. Bear

  3. Department of Physiology, University of Texas Southwestern Medical Center, Dallas, 75390, Texas, USA

    Kimberly M. Huber

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  1. Eric M. Snyder
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Correspondence to Mark F. Bear.

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Snyder, E., Philpot, B., Huber, K. et al. Internalization of ionotropic glutamate receptors in response to mGluR activation. Nat Neurosci 4, 1079–1085 (2001). https://doi.org/10.1038/nn746

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