1. Cell Biology
  2. Neuroscience

AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

  1. Josien Levenga
  2. Helen Wong
  3. Ryan A Milstead
  4. Bailey N Keller
  5. Lauren E LaPlante
  6. Charles A Hoeffer  Is a corresponding author
  1. University of Colorado, Boulder, United States
https://doi.org/10.7554/eLife.30640
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  1. Josien Levenga
  2. Helen Wong
  3. Ryan A Milstead
  4. Bailey N Keller
  5. Lauren E LaPlante
  6. Charles A Hoeffer
(2017)
AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
eLife 6:e30640.
https://doi.org/10.7554/eLife.30640
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Abstract

AKT is a kinase regulating numerous cellular processes in the brain and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.

Article and author information

Author details

  1. Josien Levenga

    Institute for Behavioral Genetics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Helen Wong

    Institute for Behavioral Genetics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Ryan A Milstead

    Department of Integrative Physiology, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Bailey N Keller

    Institute for Behavioral Genetics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Lauren E LaPlante

    Institute for Behavioral Genetics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Charles A Hoeffer

    Institute for Behavioral Genetics, University of Colorado, Boulder, Boulder, United States
    For correspondence
    charles.hoeffer@colorado.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2036-0201

Funding

Alzheimer's Association (MNIRGDP-12-258900)

  • Charles A Hoeffer

Simons Foundation (SFARI 27444)

  • Charles A Hoeffer

National Institutes of Health (R01 NS086933)

  • Charles A Hoeffer

Linda Crnic Institute Seed Grant

  • Charles A Hoeffer

Sie Foundation

  • Josien Levenga

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

Reviewing Editor

  1. Moses V Chao, New York University Langone Medical Center, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals used in this study were handled according to the approved institutional animal care and use committee (IACUC) protocols (1311.02, 2541) of the University of Colorado-Boulder.

Version history

  1. Received: July 21, 2017
  2. Accepted: November 21, 2017
  3. Accepted Manuscript published: November 27, 2017 (version 1)
  4. Version of Record published: December 8, 2017 (version 2)

Copyright

© 2017, Levenga 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. Josien Levenga
  2. Helen Wong
  3. Ryan A Milstead
  4. Bailey N Keller
  5. Lauren E LaPlante
  6. Charles A Hoeffer
(2017)
AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity
eLife 6:e30640.
https://doi.org/10.7554/eLife.30640

Share this article

https://doi.org/10.7554/eLife.30640

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