Sequencing to determine the effect of neuronal IL-1 receptor knockout and microglia depletion on stress-induced changes to the neuronal transcriptome

Chronic stress is associated with increased anxiety, cognitive deficits, and post-traumatic stress disorder. Repeated social defeat (RSD) in mice causes long-term stress-sensitization associated with increased microglia activation, monocyte accumulation, and enhanced interleukin (IL)-1 signaling in endothelia and neurons. With stress-sensitization, mice have amplified neuronal, immune, and behavioral responses to acute stress 24d later. This is clinically relevant as it shares key aspects with post-traumatic-stress-disorder. The mechanisms underlying stress-sensitization are unclear, but enhanced fear memory may be critical. The purpose of this study was to determine the influence of microglia and IL-1R1 signaling in neurons in the development of sensitization and increased fear memory after RSD. The goal of this study was to sequence nuclei from the hippocampus to determine downstream pathways of neuronal IL-1R1 (nIL-1R1) and microglia reactivity. Nuclei were isolated from hippocampi (n=3/pooled) 14hr after social defeat. 2x2: Control & Stress x Wildtype & nIL-1R1 snRNA-seq