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Polyamine-dependent facilitation of postsynaptic AMPA receptors counteracts paired-pulse depression

Abstract

At many glutamatergic synapses in the brain, calcium-permeable α - amino - 3 - hydro - 5 - methyl - 4 - isoxazolepropionate receptor (AMPAR) channels mediate fast excitatory transmission1,2,3,4,5,6. These channels are blocked by endogenous intracellular polyamines7,8,9, which are found in virtually every type of cell10,11. In excised patches, use-dependent relief of polyamine block enhances glutamate-evoked currents through recombinant and native calcium-permeable, polyamine-sensitive AMPAR channels12. The contribution of polyamine unblock to synaptic currents during high-frequency stimulation may be to facilitate currents and maintain current amplitudes in the face of a slow recovery from desensitization or presynaptic depression12,13. Here we show, on pairs and triples of synaptically connected neurons in slices, that this mechanism contributes to short-term plasticity in local circuits formed by presynaptic pyramidal neurons and postsynaptic multipolar interneurons in layer 2/3 of rat neocortex. Activity-dependent relief from polyamine block of postsynaptic calcium-permeable AMPARs in the interneurons either reduces the rate of paired-pulse depression in a frequency-dependent manner or, at a given stimulation frequency, induces facilitation of a synaptic response that would otherwise depress. This mechanism for the enhancement of synaptic gain appears to be entirely postsynaptic.

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Figure 1: Polyamine-dependent facilitation counteracts AMPAR-mediated current desensitization in outside-out patches.
Figure 2: PAs reduce amplitude and PPD of synaptic responses in multipolar interneurons but not in pyramidal cells.
Figure 3: Relief from PA block underlies enhancement of the second EPSC.
Figure 4: Physiological properties of PA-dependent facilitation of synaptic AMPAR channels in multipolar interneurons.

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Acknowledgements

We thank B. Sakmann and P. H. Seeburg for support, and F. A. Edwards and S. Robertson for reading and comments on the manuscript.

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Correspondence to Nail Burnashev.

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Rozov, A., Burnashev, N. Polyamine-dependent facilitation of postsynaptic AMPA receptors counteracts paired-pulse depression. Nature 401, 594–598 (1999). https://doi.org/10.1038/44151

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