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Postsynaptic conversion of silent synapses during LTP affects synaptic gain and transmission dynamics

Abstract

Synaptic transmission relies on both the gain and the dynamics of synapses. Activity-dependent changes in synaptic gain are well-documented at excitatory synapses and may represent a substrate for information storage in the brain. Here we examine the mechanisms of changes in transmission dynamics at excitatory synapses. We show that paired-pulse ratios (PPRs) of AMPAR and NMDAR EPSCs onto dentate gyrus granule cells are often different; this difference is reduced during LTP, reflecting PPR changes of AMPAR but not NMDAR EPSCs. Presynaptic manipulations, however, produce parallel changes in AMPAR and NMDAR EPSCs. LTP at these synapses reflects a reduction in the proportion of silent synapses lacking functional AMPARs. Changes in PPR during LTP therefore reflect the initial difference between PPRs of silent and functional synapses. Functional conversion of silent synapses permits postsynaptic sampling from additional release sites and thereby affects the dynamics and gain of signals conveyed between neurons.

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Figure 1: Non-identical paired-pulse ratios of AMPAR- and NMDAR-mediated EPSCs in dentate gyrus granule cells.
Figure 2: Pairing-induced LTP is associated with changes in paired-pulse ratios of AMPAR but not NMDAR EPSCs.
Figure 3: The amplitude and paired-pulse ratios of AMPAR and NMDAR EPSCs are similarly affected by presynaptic manipulations.
Figure 4: Pairing-induced LTP at perforant path synapses leads to a reduction of failure rate of AMPAR but not NMDAR EPSCs.
Figure 5: LTP-induced changes in paired-pulse ratios depend on the initial differences of PPR and failure rates between AMPAR and NMDAR EPSCs.
Figure 6: LTP-induced changes in transmission dynamics during repetitive stimulation.

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Acknowledgements

We thank N. Dawkins-Pisani for technical assistance, and R. Miles and Z. Mainen for reading the manuscript. This work was supported by the Human Frontier Science Program Organization (J.C.P.), the Mathers Foundation and NIH (R.M.).

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Correspondence to J. C. Poncer.

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Poncer, J., Malinow, R. Postsynaptic conversion of silent synapses during LTP affects synaptic gain and transmission dynamics. Nat Neurosci 4, 989–996 (2001). https://doi.org/10.1038/nn719

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