Affiliation:
1. The Edmond and Lily Safra Center for Brain Sciences, Jerusalem, Israel
2. Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
3. Program in Child and Brain Development, Canadian Institute for Advanced Research, MaRS Centre, Toronto, Canada
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.
Funder
Israel Science Foundation
European Research Council
The Israel Anti-Drug Administration
EU Marie Curie
National Institute for Psychobiology in Israel, Hebrew University of Jerusalem
Adelis Award for Advances in Neuroscience
Brain and Behavior Research Foundation
German-Israeli Foundation for Scientific Research and Development
US-Isral Binational Science Foundation
The Milton Rosenbaum Endowment Fund for Research in Psychiatry
Prusiner-Abramsky Research Award in Clinical and Basic Neuroscience
Jerusalem Brain Community
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience