Negative affective disturbances, including stress, anxiety, and depression, are characteristic of alcohol abstinence, and a leading cause of relapse. A greater understanding of the complex neural circuitry regulating the disease state will lead to better diagnostic tools and treatment options for abstinence-induced negative affect. This project will investigate the functional state of the insular cortex, which has been implicated in alcohol use disorders and negative affect, and two upstream regulatory inputs, the thalamus and somatosensory cortex, and dysfunction in this circuitry brought about by alcohol abstinence.
Brain and Behavior Research Foundation NARSAD Young Investigator Award
Stress regularly impacts all our lives to some degree, yet we still do not fully understand the varying degrees with which it can alter normal brain function. Stress is a unique individualized experience that can both cause a disease and exacerbate existing diseases including a particularly robust influence on neuropsychiatric diseases such as mood-, substance use-, and eating disorders. A strikingly strong correlation exists between stress and depression and anxiety, of which close to 50 million adults in the United States are diagnosed, but only 40% are successfully treated. There is an increasing need for better diagnostic tools, and alternative treatment options. While many studies focus on affective disorders once they emerge, very little is known about brain circuit activity during a stressful experience. We will use sophisticated whole brain clearing and high-resolution light sheet microscopy to image the entire intact brain and quantify which brain networks regulate stress response. Further, genetic/viral strategies will be used to isolate, genetically sequence, and circuit map stress ensembles in the insular cortex and BNST, two brain regions emerging as central integrators of the stress response circuitry. This research will provide foundational insight into, and possibly help predict, the development of affective disorders.