Bidirectional synaptic plasticity rapidly modifies hippocampal representations

  1. Aaron D Milstein
  2. Yiding Li
  3. Katie C Bittner
  4. Christine Grienberger
  5. Ivan Soltesz
  6. Jeffrey C Magee  Is a corresponding author
  7. Sandro Romani  Is a corresponding author
  1. Rutgers, The State University of New Jersey, United States
  2. Howard Hughes Medical Institute, Baylor College of Medicine, United States
  3. Howard Hughes Medical Institute, United States
  4. Stanford University, United States

Abstract

Learning requires neural adaptations thought to be mediated by activity-dependent synaptic plasticity. A relatively non-standard form of synaptic plasticity driven by dendritic calcium spikes, or plateau potentials, has been reported to underlie place field formation in rodent hippocampal CA1 neurons. Here we found that this behavioral timescale synaptic plasticity (BTSP) can also reshape existing place fields via bidirectional synaptic weight changes that depend on the temporal proximity of plateau potentials to pre-existing place fields. When evoked near an existing place field, plateau potentials induced less synaptic potentiation and more depression, suggesting BTSP might depend inversely on postsynaptic activation. However, manipulations of place cell membrane potential and computational modeling indicated that this anti-correlation actually results from a dependence on current synaptic weight such that weak inputs potentiate and strong inputs depress. A network model implementing this bidirectional synaptic learning rule suggested that BTSP enables population activity, rather than pairwise neuronal correlations, to drive neural adaptations to experience.

Data availability

The complete dataset, Python code for data analysis and model simulation, and additional MATLAB and Igor analysis scripts are available at https://github.com/neurosutras/BTSP.

The following data sets were generated

Article and author information

Author details

  1. Aaron D Milstein

    Department of Neuroscience and Cell Biology, Rutgers, The State University of New Jersey, Piscataway, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7186-5779
  2. Yiding Li

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katie C Bittner

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christine Grienberger

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ivan Soltesz

    Department of Neurosurgery, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jeffrey C Magee

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States
    For correspondence
    jcmagee@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
  7. Sandro Romani

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    romanis@janelia.hhmi.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4727-4207

Funding

National Institutes of Health (U19NS104590)

  • Aaron D Milstein
  • Ivan Soltesz

National Institute of Mental Health (R01MH121979)

  • Aaron D Milstein

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

Ethics

Animal experimentation: All experimental methods were approved by the Janelia or Baylor College of Medicine Institutional Animal Care and Use Committees (Protocol 12-84 & 15-126).

Reviewing Editor

  1. Katalin Toth, University of Ottawa, Canada

Publication history

  1. Preprint posted: February 5, 2020 (view preprint)
  2. Received: August 13, 2021
  3. Accepted: December 8, 2021
  4. Accepted Manuscript published: December 9, 2021 (version 1)
  5. Accepted Manuscript updated: December 10, 2021 (version 2)
  6. Version of Record published: January 20, 2022 (version 3)

Copyright

© 2021, Milstein 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. Aaron D Milstein
  2. Yiding Li
  3. Katie C Bittner
  4. Christine Grienberger
  5. Ivan Soltesz
  6. Jeffrey C Magee
  7. Sandro Romani
(2021)
Bidirectional synaptic plasticity rapidly modifies hippocampal representations
eLife 10:e73046.
https://doi.org/10.7554/eLife.73046
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