Neural dynamic adaptation of extended amygdala to stress and anxiety

Anxiety disorders constitute changes across behavioral, physiological, and psychological dimensions that are driven by expanse neural circuits. However, the bed nucleus of the stria terminalis (BNST), a component of the extended amygdala, plays a crucial role in regulating many aspects of these changes. For instance, activation of specific cells within BNST can drive freezing behavior and while others control physiological arousal. Still, many studies using rodent models have focused on only a handful of behavioral changes. Much of our understanding of the processes related to anxiety, consequently, have been largely based on a few phenotypes, such as avoidance of open and well-lit spaces. Here, I highlight experiments we performed to broaden our understanding of anxiety-related phenotypes and the specific BNST cell types involved. In the first aim, we measure changes in pupil size in the mouse as a proxy for arousal and find that prepronociceptin (Pnoc)-expressing neurons within BNST encode and drive these physiological changes. Further, calcium imaging indicates the cellular responses of these cells to both anxiogenic stimuli and changes in arousal are varied. This underlying heterogeneity may be the means for a broad role for BNST in controlling aspects of anxiety-related processes. For the second aim, we investigate how anxiety-like states can induce changes in behavior using more quantitative, computational analysis. We administer the alpha 2-adrenergic antagonist yohimbine to induce anxiety-like states in mice and find that these states produces a wealth of changes in behavioral expression. Further using traditional behavioral analysis would have failed to appreciate these alterations. Together, these studies highlight the advantages of taking a diverse approach to understanding anxiety-related phenotypes. The information we gain will likely accelerate our understanding of anxiety disorders and ultimately drive us toward better treatment for the disease.Doctor of Philosoph