Besides the well-known anti-inflammatory effects of glucocorticoids (GCs), these stress hormones play a key role in memory consolidation. In order to remember and in the future avoid re-encountering dangerous situation alike, GCs secreted during the stressor activate Glucocorticoid Receptors (GRs) in the brain to enhance memory consolidation. Blocking GR activation by administration of Mifepristone leads to memory impairment, confirming the role of the GR in the process. This project aims to identify the specific genes involved in GC enhanced memory consolidation. Selective GR Modulators (SGRMs) were utilized as an additional layer to select the genes involved.

Two cohorts of mice were subjected to a Cued-Fear conditioning (CFC) paradigm, followed by subcutaneous injection with either vehicle, Corticosterone, Mifepristone and SGRMs CORT108297 or CORT118335. The effect of treatment on memory consolidation was assessed by percentage freezing during retrieval in cohort I, with an increase in freezing as a measure of enhanced memory. Cohort II was sacrificed 3 hours after injection to assess the effect of acute treatment on gene expression levels. The dorsal right hippocampus was dissected and processed for RNA-sequencing to acquire transcriptome data.

The established effects of Corticosterone and Mifepristone on memory consolidation were recapitulated in the CFC paradigm in mice, evident from increased freezing after Corticosterone and decreased freezing after Mifepristone treatment. CORT118335 showed a similar effect as Mifepristone, while CORT108297 did not affect the freezing behaviour of the mice. The treatment effect of these compounds on behaviour will be combined with the transcriptome data from the parallel cohort and used as a filter to identify the genes involved in enhanced memory consolidation.