Glucocorticoids potently enhance memory consolidation after emotional events, in a strictly noradrenaline-dependent way. This suggests an interaction of two transcription factors on the genome: the glucocorticoid receptor (GR) and cAMP response binding protein (CREB). Even though the involvement of both factors has been established, their possible interactions at the genome and their transcriptional targets important for consolidation of emotional memories remain undiscovered.

Our current project focuses on identifying the binding sites of these transcription factors in the rat hippocampus, in an in vivo setting where additional GR activation acts as a switch for memory consolidation.

Male Sprague Dawley rats (n=4/group) received either object location memory (OLM) training or no training, combined with a vehicle or a 3.0mg/kg corticosterone injection (I.P.) 45 minutes prior to sacrifice. This factorial design enables to study the separate effects of OLM training (CREB activation) and corticosterone injection (GR activation) as well as their interactions. GR and CREB targeted Chromatin ImmunoPrecipitation Sequencing (ChIP-Seq) was performed on the hippocampi of these rats to identify their genomic binding sites. The genomic binding sites that were present in at least 3 out of 4 biological replicates were used in the downstream analysis and annotated to the nearest gene.

Analysis of the ChIP-Seq data reveals limited context dependence of DNA binding of both transcription factors. Due to the high basal levels of corticosterone, only a limited (<50) number of loci showed an increase in GR binding, resulting in a short-list of GR putative target genes. 8 out of 10 tested GR-binding associated genes were found to be activated by corticosterone in a separate mouse study.

These direct GR target genes may play a role in the process of glucocorticoid-enhanced memory consolidation and provides new leads to further unravel the mechanism underlying this process.