Cell-Type-Specific Molecular Signatures of Stress Resilience and Susceptibility in the Ventral Tegmental Area

Abstract

Mood disorders such as depression are prevalent mental health conditions that can cause significant disability and distress. Exposure to stressful events or chronic stress is a risk factor for developing major depression, but not all individuals who experience stress develop psychopathology. Understanding the neurogenetic basis of the variability in stress response is critical for promoting resilience and improving mental health outcomes. Preliminary results using snRNA-seq data suggest that resilience and susceptibility are associated with different gene expression changes following the administration of chronic stress. My thesis evaluates the use of RNA-fluorescence in situ hybridization (RNA-FISH) to validate gene expression changes in neurons related to susceptibility and resilience to adult chronic social stress, specifically, that resilience is associated with greater changes in gene expression than susceptibility to stress. The collection of VTA tissue from defeated mice, the optimization of RNA-FISH protocol and the consideration of candidate genes of interest from snRNA-seq data, advance our understanding of the utilization of in situ hybridization as a powerful tool for validating gene expression dynamics following stress paradigms. An understanding of molecular adaptations underlying resilience to stress could potentially lead to treatments for depression and other psychiatric disorders.