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LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1

Nature Neuroscience volume 5, pages 2733 (2002) | Download Citation

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Abstract

In the CA1 region of the rat hippocampus, long-term potentiation (LTP) requires the activation of NMDA receptors (NMDARs) and leads to an enhancement of AMPA receptor (AMPAR) function. In neonatal hippocampus, this increase in synaptic strength seems to be mediated by delivery of AMPARs to the synapse. Here we studied changes in surface expression of native AMPA and NMDA receptors following induction of LTP in the adult rat brain. In contrast to early postnatal rats, we find that LTP in the adult rat does not alter membrane association of AMPARs. Instead, LTP leads to rapid surface expression of NMDARs in a PKC- and Src-family-dependent manner. The present study suggests a developmental shift in the LTP-dependent trafficking of AMPA receptors. Moreover, our results indicate that insertion of NMDA receptors may be a key step in regulating synaptic plasticity.

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Acknowledgements

We thank M.L. Dell'Acqua, J.F. MacDonald and A.C. Spalding for advice concerning this manuscript. D.R.G. and D.A.C. are funded by individual NRSAs from NIMH. S.J.C. is supported by an individual NRSA from NIAAA. This work was also funded by NIAAA RO1 AA09675 and NIH AG04418-17.

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  1. Department of Pharmacology, University of Colorado Health Science Center, 4200 E. Ninth Ave. Box C236, Denver, Colorado 80262, USA

    • D. R. Grosshans
    • , S. J. Coultrap
    •  & M. D. Browning
  2. Medical Scientist Training Program, University of Colorado Health Science Center, 4200 E. Ninth Ave. Box C236, Denver, Colorado 80262, USA

    • D. R. Grosshans
    •  & D. A. Clayton
  3. Program in Neuroscience, University of Colorado Health Science Center, 4200 E. Ninth Ave. Box C236, Denver, Colorado 80262, USA

    • D. A. Clayton
    •  & M. D. Browning

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Competing interests

M.D.B. has a financial interest in Phosphoresolutions (Aurora, Colorado), a company that sells some of the NMDA antibodies used in this study.

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Correspondence to M. D. Browning.

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https://doi.org/10.1038/nn779

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