Stress is something everyone is familiar with. Whether it’s a traumatic event, work deadlines, illness, or a pandemic, everyone experiences “stress”. How one copes with stress depends on many factors, including past experiences, the context of the stressor, and genetic make-up. Yet, while the stressor and coping strategies employed vary from person to person, stress often has similar outcomes. Many individuals experience heightened anxiety that is often accompanied by an urge to withdraw from others. If left untreated, stress can lead to depression. How is it that such variation in stressors and individuals can manifest in similar behavioural phenotypes? And what is different in those individuals who remain resilient to stress-induced behavioural changes?

For all changes in behaviour there must exist an altered neurobiology, and for changes in neurobiology that are persistent, there must be changes in the expressions of genes coding for proteins involved in neurobiological mechanisms. To identify the neural genomic correlates of behavioural phenotypes, Caradonna et al. focused their investigation to the ventral hippocampus, a brain region that is sensitive to the impact of stress and highly implicated in affective behaviours. They applied whole-genome RNA-sequencing (RNA-seq) to identify differentially expressed genes followed by a stratified RRHO test. They found significant overlap in genes downregulated in CORT-treated mice and susceptible mice from standard housing [1], suggesting that CORT and social defeat employed similar genetic alterations to increase affective behaviours. Another intriguing result was significant overlap in genes upregulated in vehicle-treated mice and in susceptible mice from an enriched environment [1]. Enrichment shifted the overlap away from CORT-treated mice, suggesting that it protected against the genomic changes associated with stress susceptibility. While this shift was not sufficient to prevent a susceptible phenotype (as defined by social interaction scores), it is concordant with behavioural results showing reduced social avoidance in susceptible mice from an enriched environment [1].

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD