Modulation of AMPA receptor unitary conductance by synaptic activity

Abstract

Activity-dependent alteration in synaptic strength is a fundamental property of the vertebrate central nervous system and is thought to underlie learning and memory. The most extensively studied model of activity-dependent synaptic plasticity is long-term potentiation (LTP) of glutamate-responsive (glutamatergic) synapses, a widespread phenomenon involving multiple mechanisms1. The best characterized form of LTP occurs in the CA1 region of the hippocampus, in which LTP is initiated by transient activation of NMDA (N-methyl-D-aspartate) receptors and is expressed as a persistent increase in synaptic transmission through AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors2. This increase is due, at least in part, to a postsynaptic modification of AMPA-receptor function3; this modification could be caused by an increase in the number of receptors, their open probability, their kinetics or their single-channel conductance. Here we show that the induction of LTP in the CA1 region of the hippocampus is often associated with an increase in single-channel conductance of AMPA receptors. This shows that elementary channel properties can be rapidly modified by synaptic activity and provides an insight into one molecular mechanism by which glutamatergic synapses can alter their strength.

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Figure 1: Non-stationary fluctuation analysis (non-SFA) of EPSCs recorded from CA1 dendrites.
Figure 2: LTP is associated with an increase in AMPA-receptor conductance (γ).
Figure 3: A summary of changes in γ associated with LTP.
Figure 4: Increase in γ is specific to LTP.
Figure 5: Failures analysis of LTP of dendritically recorded EPSCs.

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Acknowledgements

We thank A. Silver and M. Farrant for their advice, and W. W. Anderson for providing the data acquisition software. This work was supported by the MRC (T.A.B., G.L.C.), NIH (T.A.B.), Swiss National Science Foundation (A.L.) and Wellcome Trust (J.T.R.I., G.L.C.).

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Correspondence to Graham L. Collingridge.

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Benke, T., Lüthi, A., Isaac, J. et al. Modulation of AMPA receptor unitary conductance by synaptic activity. Nature 393, 793–797 (1998). https://doi.org/10.1038/31709

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