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Maintenance of late-phase LTP is accompanied by PKA-dependent increase in AMPA receptor synthesis

Nature volume 394, pages 680–683 (1998)Cite this article

Abstract

Long-term potentiation (LTP) is a form of synaptic plasticity that has been extensively studied as a putative mechanism underlying learning and memory. A late phase of LTP occurring 3–5 hours after stimulation and depending on transcription, protein synthesis and cyclic-AMP-dependent protein kinase (protein kinase A, or PKA) has been described1,2,3, but it is not known whether transcription of presynaptic and/or postsynaptic genes is required to support late-phase LTP. Here we show that late-phase LTP can be obtained in rat hippocampal CA1 mini-slices in which the cell bodies of presynaptic Schaffer collateral/commissural fibres are removed. Thus, transcription of presynaptic genes is not necessary to support maintenance of late-phase LTP. The AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor is the predominant mediator of the ionotropic response to synaptically released glutamate in the hippocampus and it has been implicated in LTP maintenance. We find that synthesis of AMPA receptor subunits is increased three hours after LTP induction: this effect on the synthesis of the AMPA receptor is blocked by inhibitors of PKA and of transcription. Our results support the idea of a postsynaptic mechanism maintaining late-phase LTP, in which AMPA receptor synthesis is increased as a result of PKA-dependent gene transcription.

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Figure 1: Time course of LTP at various times after induction in CA1 mini-slices incubated in the absence (squares), n = 6) or presence (triangles, n = 7) of the PKA inhibitor H-89 (10 µM).
Figure 2: AMPA receptor synthesis is increased in late-phase LTP.
Figure 3: 35S-methionine/cysteine incorporation into immunoprecipitated NMDA receptor subunits NR2A, NR2B or synapsin is not significantly increased 180 min after LTP induction.
Figure 4: Quantitative western blot analysis reveals an increase in AMPA receptor subunits 180 min after LTP induction.
Figure 5: LTP-associated increased in GluR synthesis are fully blocked by RpcAMPS, H-89, actinomycin D and DRB.

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Author notes

  1. Asha Nayak, Devon J. Zastrow, Ronald Lickteig, Nancy R. Zahniser and Michael D. Browning: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pharmacology, 4200 East Ninth Avenue, Denver, 80262, Colorado, USA

    Ronald Lickteig, Nancy R. Zahniser & Michael D. Browning

  2. Neuroscience Program, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, 80262, Colorado, USA

    Asha Nayak, Devon J. Zastrow, Nancy R. Zahniser & Michael D. Browning

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  1. Asha Nayak
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Nayak, A., Zastrow, D., Lickteig, R. et al. Maintenance of late-phase LTP is accompanied by PKA-dependent increase in AMPA receptor synthesis. Nature 394, 680–683 (1998). https://doi.org/10.1038/29305

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