Abstract

Neuronal ensembles are coactive groups of cortical neurons, found in spontaneous and evoked activity, that can mediate perception and behavior. To understand the mechanisms that lead to the formation of ensembles, we co-activated layer 2/3 pyramidal neurons in brain slices from mouse visual cortex, in animals of both sexes, replicating in vitro an optogenetic protocol to generate ensembles in vivo. Using whole-cell and perforated patch-clamp pair recordings we find that, after optogenetic or electrical stimulation, coactivated neurons increase their correlated activity, a hallmark of ensemble formation. Coactivated neurons showed small biphasic changes in presynaptic plasticity, with an initial depression followed by a potentiation after a recovery period. Optogenetic and electrical stimulation also induced significant increases in frequency and amplitude of spontaneous EPSPs, even after single-cell stimulation. In addition, we observed unexpected strong and persistent increases in neuronal excitability after stimulation, with increases in membrane resistance and reductions in spike threshold. A pharmacological agent that blocks changes in membrane resistance can revert this effect. These significant increases in excitability may partly generate the observed biphasic synaptic plasticity. We propose that cell-intrinsic changes in excitability are involved in the formation of neuronal ensembles. We propose an 'iceberg' model, by which increased neuronal excitability makes subthreshold connections suprathreshold, enhancing the effect of already existing synapses, and generating a new neuronal ensemble.

Data availability

Data have been deposited with Dryad (doi:10.5061/dryad.j6q573ngc)

The following data sets were generated

Article and author information

Author details

  1. Tzitzitlini Alejandre-García

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2243-8703
  2. Samuel Kim

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jesús Pérez-Ortega

    Department of Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8502-1692
  4. Rafael Yuste

    Department of Biological Sciences, Columbia University, New York, United States
    For correspondence
    rmy5@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4206-497X

Funding

National Institute of Mental Health (R01EY011787)

  • Rafael Yuste

National Institute of Mental Health (R01MH115900)

  • Rafael Yuste

Consejo Nacional de Ciencia y Tecnología (287725)

  • Tzitzitlini Alejandre-García

Consejo Nacional de Ciencia y Tecnología

  • Jesús Pérez-Ortega

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

Reviewing Editor

  1. Lisa Giocomo, Stanford School of Medicine, United States

Ethics

Animal experimentation: All procedures were performed by following the U.S. National Institutes of Health and Columbia University Institutional Animal Care and Use Committee guidelines (IACUC, Protocol #AC-AAAV3464).

Version history

  1. Preprint posted: July 29, 2020 (view preprint)
  2. Received: January 31, 2022
  3. Accepted: May 3, 2022
  4. Accepted Manuscript published: May 4, 2022 (version 1)
  5. Version of Record published: June 14, 2022 (version 2)

Copyright

© 2022, Alejandre-García 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. Tzitzitlini Alejandre-García
  2. Samuel Kim
  3. Jesús Pérez-Ortega
  4. Rafael Yuste
(2022)
Intrinsic excitability mechanisms of neuronal ensemble formation
eLife 11:e77470.
https://doi.org/10.7554/eLife.77470

Share this article

https://doi.org/10.7554/eLife.77470

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