Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-TRAP mice

Chronic stress has become a predominant factor associated with a variety of psychiatric disorders, such as depression and anxiety, in both humans and animal models. Although multiple studies have looked at transcriptome after social defeat stress, these studies focus on bulk tissues, which could dilute important molecular signatures of social interaction activated cells.In this study, we employed the Arc-TRAP mouse model in conjunction with chronic social defeat (CSD) to selectively isolate activated nuclei (AN) populations in the ventral hippocampus (vHIP) and prefrontal cortex (PFC) brain regions of resilient and susceptible animals. We subsequently performed nuclear RNA-seq to reveal the transcriptional signatures underlying susceptible and resilient behaviors and conducted a detailed analysis on these specific populations.Our findings provide a novel view of stress-exposed neuronal activation and the molecular response mechanisms, which may have important implications for understanding the development of stress-related disorders. Overall design: Nuclear RNA-seq of activated nuclei (GFP+) and non-activated nuclei (GFP-) from Prefrontral cortex (PFC) and ventral hippocampus (vHIP) of resilience, susceptible (and control) animals following chronic social defeat.