Egr2 induction in SPNs of the ventrolateral striatum contributes to cocaine place preference in mice

  1. Diptendu Mukherjee
  2. Ben Jerry Gonzales
  3. Reut Ashwal-Fluss
  4. Hagit Turm
  5. Maya Groysman
  6. Ami Citri  Is a corresponding author
  1. The Hebrew University of Jerusalem, Israel

Abstract

Drug addiction develops due to brain-wide plasticity within neuronal ensembles, mediated by dynamic gene expression. Though the most common approach to identify such ensembles relies on immediate early gene expression, little is known of how the activity of these genes is linked to modified behavior observed following repeated drug exposure. To address this gap, we present a broad-to-specific approach, beginning with a comprehensive investigation of brain-wide cocaine-driven gene expression, through the description of dynamic spatial patterns of gene induction in subregions of the striatum, and finally address functionality of region-specific gene induction in the development of cocaine preference. Our findings reveal differential cell-type specific dynamic transcriptional recruitment patterns within two subdomains of the dorsal striatum following repeated cocaine exposure. Furthermore, we demonstrate that induction of the IEG Egr2 in the ventrolateral striatum, as well as the cells within which it is expressed, are required for the development of cocaine seeking.

Data availability

Source data file for RNA-seq and smFISH experiments are available at NCBI GEO: GSE158588, and http://dx.doi.org/10.17632/p5tsv2wpmg.1.

The following data sets were generated

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. 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.
  3. Reut Ashwal-Fluss

    The Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. 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.
  5. Maya Groysman

    The Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Ami Citri

    The Safra Center for Brain 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 (1062/18)

  • Ami Citri

Brain and Behavior Research Foundation (18795)

  • Ami Citri

German-Israeli Foundation for Scientific Research and Development (2299-2291.1/2011)

  • Ami Citri

US-Isral Binational Science Foundation (2011266)

  • Ami Citri

The Milton Rosenbaum Endowment Fund for Research in Psychiatry

  • Ami Citri

Prusiner-Abramsky Research Award in Clinical and Basic Neuroscience

  • Ami Citri

European Research Council (ERC 770951)

  • Ami Citri

Israel Science Foundation (393/12)

  • Ami Citri

Israel Science Foundation (1796/12)

  • Ami Citri

Israel Science Foundation (2341/15)

  • Ami Citri

The Israel Anti-Drug Administration

  • Ami Citri

EU Marie Curie (PCIG13-GA-2013-618201)

  • Ami Citri

National Institute for Psychobiology in Israel, Hebrew University of Jerusalem (109-15-16)

  • Ami Citri

Adelis Award for Advances in Neuroscience

  • Ami Citri

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 protocols (# NS-13-13660-3; NS-13-13895-3; NS-15-14326-3; NS-16-14644-2; NS-14667-3; NS-16-14856-3; NS-19-15753-3) were approved by the Institutional Animal Care and Use Committees at the Hebrew University of Jerusalem and were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Reviewing Editor

  1. Jeremy J Day, University of Alabama at Birmingham, United States

Publication history

  1. Received: November 26, 2020
  2. Accepted: March 15, 2021
  3. Accepted Manuscript published: March 16, 2021 (version 1)
  4. Version of Record published: April 20, 2021 (version 2)

Copyright

© 2021, 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.

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  1. Diptendu Mukherjee
  2. Ben Jerry Gonzales
  3. Reut Ashwal-Fluss
  4. Hagit Turm
  5. Maya Groysman
  6. Ami Citri
(2021)
Egr2 induction in SPNs of the ventrolateral striatum contributes to cocaine place preference in mice
eLife 10:e65228.
https://doi.org/10.7554/eLife.65228
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