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Sequential neuromodulation of Hebbian plasticity offers mechanism for effective reward-based navigation

  1. Zuzanna Brzosko
  2. Sara Zannone
  3. Wolfram Schultz
  4. Claudia Clopath
  5. Ole Paulsen  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. Imperial College London, United Kingdom
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Cite this article as: eLife 2017;6:e27756 doi: 10.7554/eLife.27756

Abstract

Spike timing-dependent plasticity (STDP) is under neuromodulatory control, which is correlated with distinct behavioral states. Previously we reported that dopamine, a reward signal, broadens the time window for synaptic potentiation and modulates the outcome of hippocampal STDP even when applied after the plasticity induction protocol (Brzosko et al., 2015). Here we demonstrate that sequential neuromodulation of STDP by acetylcholine and dopamine offers an efficacious model of reward-based navigation. Specifically, our experimental data in mouse hippocampal slices show that acetylcholine biases STDP towards synaptic depression, whilst subsequent application of dopamine converts this depression into potentiation. Incorporating this bidirectional neuromodulation-enabled correlational synaptic learning rule into a computational model yields effective navigation towards changing reward locations, as in natural foraging behavior. Thus, temporally sequenced neuromodulation of STDP enables associations to be made between actions and outcomes and also provides a possible mechanism for aligning the time scales of cellular and behavioral learning.

Article and author information

Author details

  1. Zuzanna Brzosko

    Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  2. Sara Zannone

    Department of Bioengineering, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7189-2435
  3. Wolfram Schultz

    Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    Wolfram Schultz, Reviewing Editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8530-4518
  4. Claudia Clopath

    Department of Bioengineering, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  5. Ole Paulsen

    Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    op210@cam.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2258-5455

Funding

Biotechnology and Biological Sciences Research Council (BB/N019008/1)

  • Ole Paulsen

Biotechnology and Biological Sciences Research Council (BB/N013956/1)

  • Claudia Clopath

Engineering and Physical Sciences Research Council (Studentship)

  • Sara Zannone
  • Claudia Clopath

Medical Research Council (Studentship)

  • Zuzanna Brzosko
  • Wolfram Schultz
  • Ole Paulsen

Wellcome (95495)

  • Wolfram Schultz

Wellcome (200790/Z/16/Z)

  • Claudia Clopath

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

Ethics

Animal experimentation: The research was performed under the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body (AWERB). The animal procedures were authorised under Project licence PPL 70/8892.

Reviewing Editor

  1. Marlene Bartos, University of Freiburg, Germany

Publication history

  1. Received: April 18, 2017
  2. Accepted: July 7, 2017
  3. Accepted Manuscript published: July 10, 2017 (version 1)
  4. Version of Record published: August 7, 2017 (version 2)

Copyright

© 2017, Brzosko 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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