Egr2 induction in SPNs of the ventrolateral striatum contributes to cocaine place preference in mice
- 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.
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RNA-seq of five brain structures after repeated exposure to cocaineNCBI Gene Expression Omnibus, GSE158588.
Article and author information
Author details
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.
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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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
