Hippocampal sharp wave-ripples and the associated sequence replay emerge from structured synaptic interactions in a network model of area CA3

  1. András Ecker
  2. Bence Bagi
  3. Eszter Vértes
  4. Orsolya Steinbach-Németh
  5. Maria Rita Karlocai
  6. Orsolya I Papp
  7. István Miklós
  8. Norbert Hájos
  9. Tamás Freund
  10. Attila I Gulyás
  11. Szabolcs Káli  Is a corresponding author
  1. Institute of Experimental Medicine, Hungary
  2. Alfréd Rényi Institute of Mathematics, Hungary

Abstract

Hippocampal place cells are activated sequentially as an animal explores its environment. These activity sequences are internally recreated ('replayed'), either in the same or reversed order, during bursts of activity (sharp wave-ripples; SWRs) that occur in sleep and awake rest. SWR-associated replay is thought to be critical for the creation and maintenance of long-term memory. In order to identify the cellular and network mechanisms of SWRs and replay, we constructed and simulated a data-driven model of area CA3 of the hippocampus. Our results show that the chain-like structure of recurrent excitatory interactions established during learning not only determines the content of replay, but is essential for the generation of the SWRs as well. We find that bidirectional replay requires the interplay of the experimentally confirmed, temporally symmetric plasticity rule, and cellular adaptation. Our model provides a unifying framework for diverse phenomena involving hippocampal plasticity, representations, and dynamics, and suggests that the structured neural codes induced by learning may have greater influence over cortical network states than previously appreciated.

Data availability

The source code to build, run and analyze our model is publicly available on GitHub: https://github.com/KaliLab/ca3net

Article and author information

Author details

  1. András Ecker

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9635-4169
  2. Bence Bagi

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Eszter Vértes

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Orsolya Steinbach-Németh

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. Maria Rita Karlocai

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  6. Orsolya I Papp

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  7. István Miklós

    Alfréd Rényi Institute of Mathematics, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  8. Norbert Hájos

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  9. Tamás Freund

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  10. Attila I Gulyás

    Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  11. Szabolcs Káli

    Institute of Experimental Medicine, Budapest, Hungary
    For correspondence
    kali@koki.hu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2740-6057

Funding

Hungarian Scientific Research Fund (K83251)

  • Maria Rita Karlocai
  • Attila I Gulyás
  • Szabolcs Káli

Hungarian Scientific Research Fund (K85659)

  • Orsolya Steinbach-Németh
  • Norbert Hájos

Hungarian Scientific Research Fund (K115441)

  • Attila I Gulyás
  • Szabolcs Káli

Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002)

  • Norbert Hájos

European Commission (ERC 2011 ADG 294313)

  • Tamás Freund
  • Attila I Gulyás
  • Szabolcs Káli

European Commission (FP7 no. 604102,H2020 no. 720270,no. 785907 (Human Brain Project))

  • Tamás Freund
  • Attila I Gulyás
  • Szabolcs Káli

Hungarian Ministry of Innovation and Technology NRDI Office (Artificial Intelligence National Laboratory)

  • Szabolcs Káli

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

Ethics

Animal experimentation: Experiments were approved by the Committee for the Scientific Ethics of Animal Research (22.1/4027/003/2009) and were performed according to the guidelines of the institutional ethical code and the Hungarian Act of Animal Care and Experimentation. Experiments were performed in acute brain slices; no animal suffering was involved as mice were deeply anaesthetized with isoflurane and decapitated before slice preparation. Data recorded in the context of other studies were used for model fitting, and therefore no additional animals were used for the purpose of this study.

Reviewing Editor

  1. Neil Burgess, University College London, United Kingdom

Publication history

  1. Preprint posted: February 18, 2021 (view preprint)
  2. Received: July 2, 2021
  3. Accepted: January 17, 2022
  4. Accepted Manuscript published: January 18, 2022 (version 1)
  5. Version of Record published: February 23, 2022 (version 2)

Copyright

© 2022, Ecker 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. András Ecker
  2. Bence Bagi
  3. Eszter Vértes
  4. Orsolya Steinbach-Németh
  5. Maria Rita Karlocai
  6. Orsolya I Papp
  7. István Miklós
  8. Norbert Hájos
  9. Tamás Freund
  10. Attila I Gulyás
  11. Szabolcs Káli
(2022)
Hippocampal sharp wave-ripples and the associated sequence replay emerge from structured synaptic interactions in a network model of area CA3
eLife 11:e71850.
https://doi.org/10.7554/eLife.71850

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