Salient experiences are represented by unique transcriptional signatures in the mouse brain

  1. Diptendu Mukherjee
  2. Bogna Marta Ignatowska-Jankowska
  3. Eyal Itskovits
  4. Ben Jerry Gonzales
  5. Hagit Turm
  6. Liz Izakson
  7. Doron Haritan
  8. Noa Bleistein
  9. Chen Cohen
  10. Ido Amit
  11. Tal Shay
  12. Brad Grueter
  13. Alon Zaslaver
  14. Ami Citri  Is a corresponding author
  1. The Hebrew University of Jerusalem, Israel
  2. Weizmann Institute of Science, Israel
  3. Ben-Gurion University of the Negev, Israel
  4. Vanderbilt University School of Medicine, United States

Abstract

It is well established that inducible transcription is essential for the consolidation of salient experiences into long-term memory. However, whether inducible transcription relays information about the identity and affective attributes of the experience being encoded, has not been explored. To this end, we analyzed transcription induced by a variety of rewarding and aversive experiences, across multiple brain regions. Our results describe the existence of robust transcriptional signatures uniquely representing distinct experiences, enabling near-perfect decoding of recent experiences. Furthermore, experiences with shared attributes display commonalities in their transcriptional signatures, exemplified in the representation of valence, habituation and reinforcement. This study introduces the concept of a neural transcriptional code, which represents the encoding of experiences in the mouse brain. This code is comprised of distinct transcriptional signatures that correlate to attributes of the experiences that are being committed to long-term memory.

Article and author information

Author details

  1. Diptendu Mukherjee

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Bogna Marta Ignatowska-Jankowska

    The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Eyal Itskovits

    Department of Genetics, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Ben Jerry Gonzales

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Hagit Turm

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Liz Izakson

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Doron Haritan

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Noa Bleistein

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  9. Chen Cohen

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  10. Ido Amit

    Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  11. Tal Shay

    Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.
  12. Brad Grueter

    Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4224-3866
  13. Alon Zaslaver

    Department of Genetics, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  14. Ami Citri

    Department of Biological Chemistry, Silberman Institute for Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    For correspondence
    ami.citri@mail.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9914-0278

Funding

Israel Science Foundation (Personal Grant 393/12 & I-CORE 1796/12)

  • Ami Citri

The Lady Davis Postdoctoral Fellowship (Postdoctoral stipend)

  • Bogna Marta Ignatowska-Jankowska

German-Israeli Foundation for Scientific Research and Development (Young Investigator Award 2299-2291.1./2011)

  • Ami Citri

Brain and Behavior Research Foundation (Young Investigator Award #18795)

  • Ami Citri

Canadian Institute for Advanced Research (Research Support)

  • Ami Citri

Binational United-States Israel Research Foundation (Research Grant #2011266)

  • Ami Citri

Milton Rosenbaum Research Foundation (Research Grant)

  • Ami Citri

National Institutes for Psychobiology in Israel (Research Grant 109-15-16)

  • Ami Citri

Shimon Peres Postdoctoral Award (Postdoctoral stipend)

  • Bogna Marta Ignatowska-Jankowska

ELSC Postdoctoral Award (Postdoctoral stipend)

  • Bogna Marta Ignatowska-Jankowska

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

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 of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#NS-13-13895-3 ; NS-15-14668-3 ; NS-14-14088-3 ; NS-15-14312-3 ; NS-15-14348-3) of the Hebrew University of Jerusalem. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Hebrew University. Every effort was made to minimize suffering.

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Publication history

  1. Received: September 4, 2017
  2. Accepted: February 5, 2018
  3. Accepted Manuscript published: February 7, 2018 (version 1)
  4. Accepted Manuscript updated: February 22, 2018 (version 2)
  5. Version of Record published: March 21, 2018 (version 3)

Copyright

© 2018, Mukherjee 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.

Metrics

  • 6,348
    Page views
  • 1,002
    Downloads
  • 22
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Diptendu Mukherjee
  2. Bogna Marta Ignatowska-Jankowska
  3. Eyal Itskovits
  4. Ben Jerry Gonzales
  5. Hagit Turm
  6. Liz Izakson
  7. Doron Haritan
  8. Noa Bleistein
  9. Chen Cohen
  10. Ido Amit
  11. Tal Shay
  12. Brad Grueter
  13. Alon Zaslaver
  14. Ami Citri
(2018)
Salient experiences are represented by unique transcriptional signatures in the mouse brain
eLife 7:e31220.
https://doi.org/10.7554/eLife.31220
  1. Further reading

Further reading

    1. Developmental Biology
    2. Neuroscience
    Ashtyn T Wiltbank et al.
    Research Article

    Efficient neurotransmission is essential for organism survival and is enhanced by myelination. However, the genes that regulate myelin and myelinating glial cell development have not been fully characterized. Data from our lab and others demonstrates that cd59, which encodes for a small GPI-anchored glycoprotein, is highly expressed in developing zebrafish, rodent, and human oligodendrocytes (OLs) and Schwann cells (SCs), and that patients with CD59 dysfunction develop neurological dysfunction during early childhood. Yet, the function of Cd59 in the developing nervous system is currently undefined. In this study, we demonstrate that cd59 is expressed in a subset of developing SCs. Using cd59 mutant zebrafish, we show that developing SCs proliferate excessively and nerves may have reduced myelin volume, altered myelin ultrastructure, and perturbed node of Ranvier assembly. Finally, we demonstrate that complement activity is elevated in cd59 mutants and that inhibiting inflammation restores SC proliferation, myelin volume, and nodes of Ranvier to wildtype levels. Together, this work identifies Cd59 and developmental inflammation as key players in myelinating glial cell development, highlighting the collaboration between glia and the innate immune system to ensure normal neural development.

    1. Neuroscience
    Arefeh Sherafati et al.
    Research Article Updated

    Cochlear implants are neuroprosthetic devices that can restore hearing in people with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of acoustic detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging data in this population. In the current study, we assessed the brain regions supporting spoken word understanding in adult listeners with right unilateral cochlear implants (n=20) and matched controls (n=18) using high-density diffuse optical tomography (HD-DOT), a quiet and non-invasive imaging modality with spatial resolution comparable to that of functional MRI. We found that while listening to spoken words in quiet, listeners with cochlear implants showed greater activity in the left prefrontal cortex than listeners with normal hearing, specifically in a region engaged in a separate spatial working memory task. These results suggest that listeners with cochlear implants require greater cognitive processing during speech understanding than listeners with normal hearing, supported by compensatory recruitment of the left prefrontal cortex.