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A proportional but slower NMDA potentiation follows AMPA potentiation in LTP

Nature Neuroscience volume 7, pages 518–524 (2004)Cite this article

Abstract

Most excitatory glutamatergic synapses contain both AMPA and NMDA receptors, but whether these receptors are regulated together or independently during synaptic plasticity has been controversial. Although long-term potentiation (LTP) is thought to selectively enhance AMPA currents and alter the NMDA-to-AMPA ratio, this ratio is well conserved across synapses onto the same neuron. This suggests that the NMDA-to-AMPA ratio is only transiently perturbed by LTP. To test this, we induced LTP at rat neocortical synapses and recorded mixed AMPA-NMDA currents. We observed rapid LTP of AMPA currents, as well as delayed potentiation of NMDA currents that required previous AMPA potentiation. The delayed potentiation of NMDA currents restored the original NMDA-to-AMPA ratio within 2 h of LTP induction. These data suggest that recruitment of AMPA receptors to synapses eventually induces a proportional increase in NMDA current. This may ensure that LTP does not alter the relative contributions of these two receptors to synaptic transmission and information processing.

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Figure 1: Long-term potentiation of mEPSCs.
Figure 2: Delayed NMDA-LTP restores the NMDA-to-AMPA ratio.
Figure 3: Correlation between the AMPA and NMDA amplitudes of individual mEPSCs.
Figure 4: Delayed NMDA-LTP does not require post-induction activity or glutamate receptor activation, but requires AMPA-LTP.
Figure 5: Delayed and proportional NMDA-LTP at a unitary connection between layer 5 pyramidal neurons.
Figure 6: Summary data from layer-5 unitary synapses.

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Acknowledgements

We thank M. Hermann for the preparation of cultures. The GFP-GluR1 carboxy tail construct was a gift from R. Malinow. This work was supported by the National Institute of Neurological Diseases and Stroke (36853), the Eye Institute (11116) and a Wellcome Trust Senior Fellowship to M.H.

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Authors and Affiliations

  1. Department of Biology and Volen National Center for Complex Systems, MS 08, 415 South Street, Brandeis University, Waltham, 02454, Massachusetts, USA

    Alanna J Watt, Per Jesper Sjöström, Sacha B Nelson & Gina G Turrigiano

  2. Wolfson Institute for Biomedical Research and Department of Physiology, University College London, Gower Street, London, WC1E 6BT, UK

    Alanna J Watt, Per Jesper Sjöström & Michael Häusser

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Correspondence to Gina G Turrigiano.

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Watt, A., Sjöström, P., Häusser, M. et al. A proportional but slower NMDA potentiation follows AMPA potentiation in LTP. Nat Neurosci 7, 518–524 (2004). https://doi.org/10.1038/nn1220

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