Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

Abstract

Locomotor sensitization (LS) is an early behavioral adaptation to addictive drugs, driven by the increase of dopamine in the Nucleus Accumbens (NAc). However, the effect on accumbal population activity remains elusive. Here we used single cell calcium imaging in mice to record the activity of dopamine-1-receptor (D1R) and dopamine-2-receptor (D2R) expressing spiny projection neurons (SPNs) during cocaine LS. Acute exposure to cocaine elevated D1R SPN activity and reduced D2R SPN activity, albeit with high variability between neurons. During LS, the number of D1R and D2R neurons responding in opposite directions increased. Moreover, preventing LS by inhibition of the ERK signaling pathway decreased the number of cocaine responsive D1R SPNs, but had little effect on D2R SPNs. These results indicate that accumbal population dichotomy is dynamic and contains a subgroup of D1R SPNs that eventually drives LS. Insights into the drug-related activity dynamics provides a foundation for understanding the circuit-level addiction pathogenesis.

Data availability

Data and code have been made available via Zenodo: DOI: 10.5281/zenodo.5507009

The following data sets were generated

Article and author information

Author details

  1. Ruud van Zessen

    Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5634-6922
  2. Yue Li

    Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Lucile Marion-Poll

    Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicolas Hulo

    Service for Biomathematical and Biostatistical Analyses, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2640-636X
  5. Jérôme Flakowski

    Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6457-3022
  6. Christian Lüscher

    Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland
    For correspondence
    Christian.Luscher@unige.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7917-4596

Funding

Swiss National Science Foundation (310030_189188)

  • Christian Lüscher

European Commission (F_Addict)

  • Christian Lüscher

Swiss National Science Foundation (CRSII5_186266)

  • Christian Lüscher

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

Reviewing Editor

  1. Aryn H Gittis, Carnegie Mellon University, United States

Ethics

Animal experimentation: All experiments were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Geneva (GE64-20 and GE71-20)

Version history

  1. Received: December 23, 2020
  2. Preprint posted: January 30, 2021 (view preprint)
  3. Accepted: September 28, 2021
  4. Accepted Manuscript published: October 5, 2021 (version 1)
  5. Accepted Manuscript updated: October 6, 2021 (version 2)
  6. Version of Record published: October 18, 2021 (version 3)

Copyright

© 2021, van Zessen 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. Ruud van Zessen
  2. Yue Li
  3. Lucile Marion-Poll
  4. Nicolas Hulo
  5. Jérôme Flakowski
  6. Christian Lüscher
(2021)
Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
eLife 10:e66048.
https://doi.org/10.7554/eLife.66048

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https://doi.org/10.7554/eLife.66048

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