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Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity

Author

Listed:
  • Hey-Kyoung Lee

    (Johns Hopkins Medical School)

  • Michaela Barbarosie

    (Howard Hughes Medical Institute, Brown University)

  • Kimihiko Kameyama

    (Laboratory of Molecular Neurobiology, National Institute of Bioscience and Human Technology)

  • Mark F. Bear

    (Howard Hughes Medical Institute, Brown University)

  • Richard L. Huganir

    (Johns Hopkins Medical School)

Abstract

Bidirectional changes in the efficacy of neuronal synaptic transmission, such as hippocampal long-term potentiation (LTP) and long-term depression (LTD), are thought to be mechanisms for information storage in the brain1,2,3,4. LTP and LTD may be mediated by the modulation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazloe proprionic acid) receptor phosphorylation5,6,7. Here we show that LTP and LTD reversibly modify the phosphorylation of the AMPA receptor GluR1 subunit. However, contrary to the hypothesis that LTP and LTD are the functional inverse of each other, we find that they are associated with phosphorylation and dephosphorylation, respectively, of distinct GluR1 phosphorylation sites. Moreover, the site modulated depends on the stimulation history of the synapse. LTD induction in naive synapses dephosphorylates the major cyclic-AMP-dependent protein kinase (PKA) site, whereas in potentiated synapses the major calcium/calmodulin-dependent protein kinase II (CaMKII) site is dephosphorylated. Conversely, LTP induction in naive synapses and depressed synapses increases phosphorylation of the CaMKII site and the PKA site, respectively. LTP is differentially sensitive to CaMKII and PKA inhibitors depending on the history of the synapse. These results indicate that AMPA receptor phosphorylation is critical for synaptic plasticity, and that identical stimulation conditions recruit different signal-transduction pathways depending on synaptic history.

Suggested Citation

  • Hey-Kyoung Lee & Michaela Barbarosie & Kimihiko Kameyama & Mark F. Bear & Richard L. Huganir, 2000. "Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity," Nature, Nature, vol. 405(6789), pages 955-959, June.
    • Handle: RePEc:nat:nature:v:405:y:2000:i:6789:d:10.1038_35016089
    DOI: 10.1038/35016089
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