Satb2 determines miRNA expression and long-term memory in the adult central nervous system

  1. Clemens Jaitner
  2. Chethan Reddy
  3. Andreas Abentung
  4. Nigel Whittle
  5. Dietmar Rieder
  6. Andrea Delekate
  7. Martin Korte
  8. Gaurav Jain
  9. Andre Fischer
  10. Farahnaz Sananbenesi
  11. Isabella Cera
  12. Nicolas Singewald
  13. Georg Dechant  Is a corresponding author
  14. Galina Apostolova  Is a corresponding author
  1. Medical University of Innsbruck, Austria
  2. University of Innsbruck, Austria
  3. Technical University Braunschweig, Germany
  4. German Center for Neurodegenerative Diseases, Germany

Abstract

SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

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The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Clemens Jaitner

    Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  2. Chethan Reddy

    Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Andreas Abentung

    Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Nigel Whittle

    Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Dietmar Rieder

    Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  6. Andrea Delekate

    Zoological Institute, Technical University Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8887-0806
  7. Martin Korte

    Zoological Institute, Technical University Braunschweig, Braunschweig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Gaurav Jain

    Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Andre Fischer

    Research group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Farahnaz Sananbenesi

    Research group for Complex Neurodegenerative Disorders, German Center for Neurodegenerative Diseases, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Isabella Cera

    Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  12. Nicolas Singewald

    Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria
    Competing interests
    The authors declare that no competing interests exist.
  13. Georg Dechant

    Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria
    For correspondence
    georg.dechant@i-med.ac.at
    Competing interests
    The authors declare that no competing interests exist.
  14. Galina Apostolova

    Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria
    For correspondence
    galina.apostolova@i-med.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2682-4385

Funding

Austrian Science Fund (P25014-B24)

  • Galina Apostolova

Austrian Science Fund (DK W1206)

  • Georg Dechant

Austrian Science Fund (DK W1206)

  • Nicolas Singewald

Deutsche Forschungsgemeinschaft

  • Martin Korte

Innsbruck Medical University (MUI-Start 2010012004)

  • Galina Apostolova

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 animal experimentation procedures were approved by the Austrian Animal Experimentation Ethics Board (Permit Number: GZ: BMWFW-66.011/0078-WF/II/3b/2014)

Reviewing Editor

  1. Anne West, Duke University School of Medicine, United States

Publication history

  1. Received: April 28, 2016
  2. Accepted: November 28, 2016
  3. Accepted Manuscript published: November 29, 2016 (version 1)
  4. Version of Record published: January 3, 2017 (version 2)

Copyright

© 2016, Jaitner 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. Clemens Jaitner
  2. Chethan Reddy
  3. Andreas Abentung
  4. Nigel Whittle
  5. Dietmar Rieder
  6. Andrea Delekate
  7. Martin Korte
  8. Gaurav Jain
  9. Andre Fischer
  10. Farahnaz Sananbenesi
  11. Isabella Cera
  12. Nicolas Singewald
  13. Georg Dechant
  14. Galina Apostolova
(2016)
Satb2 determines miRNA expression and long-term memory in the adult central nervous system
eLife 5:e17361.
https://doi.org/10.7554/eLife.17361

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