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Use-dependent AMPA receptor block in mice lacking GluR2 suggests postsynaptic site for LTP expression

Nature Neuroscience volume 1, pages 579–586 (1998)Cite this article

Abstract

The mechanisms responsible for enhanced transmission during long-term potentiation (LTP) at CA1 hippocampal synapses remain elusive. Several popular models for LTP expression propose an increase in 'use' of existing synaptic elements, such as increased probability of transmitter release or increased opening of postsynaptic receptors. To test these models directly, we studied a GluR2 knockout mouse in which AMPA receptor transmission is rendered sensitive to a use-dependent block by polyamine compounds. This method can detect increases during manipulations affecting transmitter release or AMPA receptor channel open time and probability, but shows no such changes during LTP. Our results indicate that the recruitment of new AMPA receptors and/or an increase in the conductance of these receptors is responsible for the expression of CA1 LTP.

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Figure 1: Selective block of AMPA-receptor-mediated synaptic transmission by HPP-SP in GluR2–/– mice.
Figure 2: Block by HPP-SP in GluR2–/– mice is use dependent and reversible.
Figure 3: Enhancement of presynaptic or postsynaptic use increases block by HPP-SP.
Figure 4: Whole-cell experiments show similar increases in amplitude and quantal content following pairing-induced LTP in GluR2–/– mice.
Figure 5: Field experiments show predominant change in AMPA receptor transmission during LTP in GluR2–/– mice.
Figure 6: Long-term potentiation produces no change in block by HPP-SP.
Figure 7: Analytical model showing expected change in HPP-SP block for a shift in Pr distribution.
Figure 8: Summary of effects of experimental manipulations on HPP-SP block.

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Acknowledgements

We thank H. Cline, K. Svoboda and members of the Malinow lab for comments on the manuscript and Y. Hayashi and N. Dawkins for assistance in genotyping. Supported by N.I.H. and Mathers Foundation (R.M.) and a Burroughs Wellcome Fund Career Award (Z. F. M.).

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Authors and Affiliations

  1. Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, 11724, New York, USA

    Zachary F. Mainen & Roberto Malinow

  2. Mount Sinai Hospital Research Inst., 600 University Ave., Toronto, M5G1X5, Ontario, Canada

    Zhengping Jia & John Roder

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Correspondence to Zachary F. Mainen.

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Mainen, Z., Jia, Z., Roder, J. et al. Use-dependent AMPA receptor block in mice lacking GluR2 suggests postsynaptic site for LTP expression. Nat Neurosci 1, 579–586 (1998). https://doi.org/10.1038/2812

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