1. Neuroscience
Download icon

Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

Research Article
  • Cited 1
  • Views 1,142
  • Annotations
Cite this article as: eLife 2021;10:e66048 doi: 10.7554/eLife.66048

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.

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)

Reviewing Editor

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

Publication 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.

Metrics

  • 1,142
    Page views
  • 174
    Downloads
  • 1
    Citations

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

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)

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

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

Further reading

    1. Neuroscience
    Wucheng Tao et al.
    Research Article Updated

    Long-term potentiation (LTP) is arguably the most compelling cellular model for learning and memory. While the mechanisms underlying the induction of LTP (‘learning’) are well understood, the maintenance of LTP (‘memory’) has remained contentious over the last 20 years. Here, we find that Ca2+-calmodulin-dependent kinase II (CaMKII) contributes to synaptic transmission and is required LTP maintenance. Acute inhibition of CaMKII erases LTP and transient inhibition of CaMKII enhances subsequent LTP. These findings strongly support the role of CaMKII as a molecular storage device.

    1. Medicine
    2. Neuroscience
    Zifei Liang et al.
    Tools and Resources

    1H MRI maps brain structure and function non-invasively through versatile contrasts that exploit inhomogeneity in tissue micro-environments. Inferring histopathological information from MRI findings, however, remains challenging due to absence of direct links between MRI signals and cellular structures. Here, we show that deep convolutional neural networks, developed using co-registered multi-contrast MRI and histological data of the mouse brain, can estimate histological staining intensity directly from MRI signals at each voxel. The results provide three-dimensional maps of axons and myelin with tissue contrasts that closely mimics target histology and enhanced sensitivity and specificity compared to conventional MRI markers. Furthermore, the relative contribution of each MRI contrast within the networks can be used to optimize multi-contrast MRI acquisition. We anticipate our method to be a starting point for translation of MRI results into easy-to-understand virtual histology for neurobiologists and provide resources for validating novel MRI techniques.