Glutamate is required for depression but not potentiation of long-term presynaptic function

  1. Zahid Padamsey  Is a corresponding author
  2. Rudi Tong
  3. Nigel Emptage  Is a corresponding author
  1. University of Oxford, United Kingdom

Abstract

Hebbian plasticity is thought to require glutamate signalling. We show this is not the case for hippocampal presynaptic long-term potentiation (LTPpre), which is expressed as an increase in transmitter release probability (Pr). We find that LTPpre can be induced by pairing pre- and postsynaptic spiking in the absence of glutamate signalling. LTPpre induction involves a non-canonical mechanism of retrograde nitric oxide signalling, which is triggered by Ca2+ influx from L-type voltage-gated Ca2+ channels, not postsynaptic NMDA receptors (NMDARs), and does not require glutamate release. When glutamate release occurs, it decreases Pr by activating presynaptic NMDARs, and promotes presynaptic long-term depression. Net changes in Pr, therefore, depend on two opposing factors: 1) Hebbian activity, which increases Pr, and 2) glutamate release, which decreases Pr. Accordingly, release failures during Hebbian activity promote LTPpre induction. Our findings reveal a novel framework of presynaptic plasticity that radically differs from traditional models of postsynaptic plasticity.

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Author details

  1. Zahid Padamsey

    Department of Pharmacology, University of Oxford, Oxford, United Kingdom
    For correspondence
    zahid.padamsey@pharm.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9177-8210
  2. Rudi Tong

    Department of Pharmacology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Nigel Emptage

    Department of Pharmacology, University of Oxford, Oxford, United Kingdom
    For correspondence
    nigel.emptage@pharm.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7348-497X

Funding

Medical Research Council

  • Nigel Emptage

Biotechnology and Biological Sciences Research Council

  • Nigel Emptage

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Padamsey et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Zahid Padamsey
  2. Rudi Tong
  3. Nigel Emptage
(2017)
Glutamate is required for depression but not potentiation of long-term presynaptic function
eLife 6:e29688.
https://doi.org/10.7554/eLife.29688

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https://doi.org/10.7554/eLife.29688