Egr2 induction in spiny projection neurons of the ventrolateral striatum contributes to cocaine place preference in mice

eLife

Reut Ashwal-Fluss¹  Maya Groysman¹  Hagit Turm²  Ben Jerry Gonzales²  Diptendu Mukherjee²  Ami Citri³ 

[1] The Edmond and Lily Safra Center for Brain Sciences, Jerusalem, Israel;The Edmond and Lily Safra Center for Brain Sciences, Jerusalem, Israel;Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel;The Edmond and Lily Safra Center for Brain Sciences, Jerusalem, Israel;Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel;Program in Child and Brain Development, Canadian Institute for Advanced Research, MaRS Centre, Toronto, Canada;

关键词: striatum;    cocaine;    reward;    ensembles;    IEG;    transcriptomics;    Mouse;   

DOI  :  10.7554/eLife.65228

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY