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

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.

Early-life stress and ovarian hormones alter transcriptional regulation in the nucleus accumbens resulting in sex-specific responses to cocaine

“…For example, cocaine increases chromatin accessibility in a region upstream of Esr2 , encoding ERβ, specifically in diestrus females ( Figure 5C and Table S4 ). We also observed diestrus-specific DARs at the promoters of Ezh2 , encoding a histone methyltransferase, and Egr2 , encoding early-growth response 2, an immediate-early gene critical for establishing cocaine-induced CPP 80 ( Figure 5C and Table S4 ). In summary, males and diestrus females exhibit similar changes in cocaine accessibility in genes related to GABAergic function but also have divergent responses, with male-specific DARs observed at dopamine receptor genes and diestrus-specific DARs observed at estrogen signaling-related genes.…”

Young transposable elements rewired gene regulatory networks in human and chimpanzee hippocampal intermediate progenitors

“…5 A,C). EGR2 is an early response gene involved in learning and memory, in the brain response to stimuli and in hippocampal synaptic plasticity ( Cheval et al, 2012 ; Mukherjee et al, 2021 ; Poirier et al, 2007 ). CTCF, a well-known regulator of chromatin structure, has been implicated in various neurodevelopmental disorders (reviewed by Davis et al, 2018 ).…”

Nicotine, THC, and Dolutegravir Modulate E-Cigarette-Induced Changes in Addiction- and Inflammation-Associated Genes in Rat Brains and Astrocytes

“…Alterations in EGR2 and ARC are found in addiction models [25,31,[34][35][36]. Changes in ARC are induced rapidly, in as little as 30 min [24], following psychoactive substance administration, with increases sustained chronically [31,37], and decreases induced by psychoactive substance withdrawal [31,37].…”