1. Neuroscience
Download icon

Dynamic dichotomy of accumbal population activity underlies cocaine sensitization

Research Article
  • Cited 0
  • Views 700
  • 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. Accepted: September 28, 2021
  3. Accepted Manuscript published: October 5, 2021 (version 1)
  4. Accepted Manuscript updated: October 6, 2021 (version 2)

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

  • 700
    Page views
  • 120
    Downloads
  • 0
    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. Cell Biology
    2. Neuroscience
    Zhong-Jiao Jiang et al.
    Research Article Updated

    Transient receptor potential melastatin 7 (TRPM7) contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in central nervous system (CNS) neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmissions from TRPM7 KO mice. Taken together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.

    1. Neuroscience
    Renée S Koolschijn et al.
    Research Article Updated

    The brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism.