1. Neuroscience
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Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits

Research Article
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Cite this article as: eLife 2018;7:e33092 doi: 10.7554/eLife.33092

Abstract

Sensory experience plays an important role in shaping neural circuitry by affecting the synaptic connectivity and intrinsic properties of individual neurons. Identifying the molecular players responsible for converting external stimuli into altered neuronal output remains a crucial step in understanding experience-dependent plasticity and circuit function. Here, we investigate the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in visual circuit plasticity. We demonstrate that Rem2-/- mice fail to exhibit normal ocular dominance plasticity during the critical period. At the cellular level, our data establish a cell-autonomous role for Rem2 in regulating intrinsic excitability of layer 2/3 pyramidal neurons, prior to changes in synaptic function. Consistent with these findings, both in vitro and in vivo recordings reveal increased spontaneous firing rates in the absence of Rem2. Taken together, our data demonstrate that Rem2 is a key molecule that regulates neuronal excitability and circuit function in the context of changing sensory experience.

Data availability

Imaging data is available at http://www.vhlab.org/data.All other data generated or analyzed during this study is included in the manuscript and supporting files.

Article and author information

Author details

  1. Anna R Moore

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sarah E Richards

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katelyn Kenny

    National Center for Behavioral Genomics, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Leandro Royer

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Urann Chan

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kelly Flavahan

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephen D Van Hooser

    Department of Biology, Brandeis University, Waltham, United States
    For correspondence
    vanhoosr@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1112-5832
  8. Suzanne Paradis

    Department of Biology, Brandeis University, Waltham, United States
    For correspondence
    paradis@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5190-4240

Funding

National Eye Institute (EY022122)

  • Stephen D Van Hooser

National Institute of Mental Health (K01MH101639)

  • Anna R Moore

National Institute of Neurological Disorders and Stroke (R01NS065856)

  • Suzanne Paradis

National Institute of Neurological Disorders and Stroke (Ruth L Kirschstein NIH Training Grant T32NS007292)

  • Anna R Moore

Charles Hood Foundation

  • Stephen D Van Hooser

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 procedures involving animals were performed in strict accordance with the recommendations set forth in the Guide for the Care and Use of Laboratory Animals of the National Institute of Health. All animal handling and experimental procedures were approved by the Institutional Animal Care and Use Committee at Brandeis University (Protocol Numbers: 16002 and 17004). Surgical procedures were performed under sterile conditions and every effort was made to minimize suffering.

Reviewing Editor

  1. Yukiko Goda, RIKEN, Japan

Publication history

  1. Received: October 25, 2017
  2. Accepted: May 28, 2018
  3. Accepted Manuscript published: May 29, 2018 (version 1)
  4. Version of Record published: June 20, 2018 (version 2)

Copyright

© 2018, Moore 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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