Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
- University of Geneva, Switzerland
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
-
Dynamic dichotomy of accumbal population activity underlies cocaine sensitizationZenodo, DOI: 10.5281/zenodo.5507009.
Article and author information
Author details
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)
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
-
- 2,576
- views
-
- 403
- downloads
-
- 24
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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)
Dynamic dichotomy of accumbal population activity underlies cocaine sensitization
eLife 10:e66048.
https://doi.org/10.7554/eLife.66048
Further reading
-
- Neuroscience
γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here, we employ the near-infrared (NIR) C99 720–670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential ‘cell non-autonomous’ regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.
-
- Neuroscience
The neurotransmitter dopamine helps form long-term memories by increasing the production of proteins through a unique signaling pathway.
