Social experience dependent modification of gene regulation and circuit function

Social isolation has profound effects on animal behaviors and physiological responses. Loneliness has been linked to various detrimental effects on the brain, including an increased incidence of neuropsychiatric disease and dementia. However, the precise molecular and neural mechanisms through which social isolation influences brain health and behaviors remain elusive. Recent data suggest an immune and neuroinflammatory basis for precipitating neuropsychiatric and neurodegenerative disorders. We hypothesize that transcriptional changes in immune gene expression and immune state in the brain contribute to social experience-dependent modulation of behavior. Consistent with this hypothesis, our preliminary studies have identified alterations in immune gene expression and the blood-brain barrier-a critical immune structure in the brain-in response to social isolation. This proposal aims to uncover the underlying transcriptional, cellular, and circuit mechanisms that mediate the impact of social isolation on brain immunity and behavioral responses. We will test the hypothesis that distinct pheromone circuits communicate social signals to the brain, reprogramming transcription, immune gene expression, and immune responses to modulate courtship behaviors with social experience. First, we will identify the neurons and glia that express the socially regulated immune genes in the central brain and the pheromone circuits modulating their expression with social experience. Next, we will determine how the immune state of the brain changes with social experience, along with identifying the pheromone circuits mediating these effects. Finally, we will investigate whether social modulation of immune gene expression and immune state contributes to social experience-dependent modulation of courtship behaviors. We expect the results from our studies to have immense potential for the development of strategies to mitigate the adverse effects brought about by social isolation on brain health and behavior. Project Summary/Abstract