Prefrontal influences on the midbrain periaqueductal gray in modulating stress coping responses 

How does the brain coordinate all of the complex systems to orchestrate coherent responses to threats from the environment? This set of responses is called stress coping, and it shows specific patterns in animals and humans depending on whether they are engaged in active or passive responses. Our research has revealed an important role for the prefrontal cortex in coordinating stress hormonal, autonomic, and behavioral response features in responses to threatening stimuli in both male and female rats, through this brain region’s interaction with the midbrain periaqueductal gray. In this line of investigation, we are exploring the relationship between the prefrontal cortex–periaqueductal gray pathway’s regulation of stress coping responses vis-à-vis the periaqueductal gray itself, and other upstream limbic regions, such as the central amygdala. Our long-term goal is to gain basic insights into how malfunctioning in these pathways, such as following traumatic or chronic stress, may improve our understanding of the underlying neural bases leading to stress related mental disorders in humans.  

The role of circuit versus stress hormonal influences in the consolidation of aversive memories

Discrimination between threatening and non-threatening contexts is an adaptive neurobiological process, whereas traumatic stressors may shift responses toward generalization. From a translational perspective, the loss of discrimination, or over-generalization, from a stressful to neutral context is one of the core features of stress-related psychiatric diseases. To date, many studies have made inroads in understanding memory consolidation processes in terms of overall memory strength, yet the post-learning processes that underlie discrimination versus generalization remain poorly understood. Our work data suggests that limbic forebrain influences over the anteroventral bed nuclei of the stria terminalis (BST) are positioned to differentially regulate memory strength and discrimination following an aversive learning paradigm. In this manner, the medial prefrontal cortical projection to the BST in rats plays an important role in promoting memory consolidation that results in an enhanced ability to discriminate between threatening and neutral contexts during future encounters. Our ongoing work seeks to differentiate the role of stress hormones in altering consolidation via influencing BST-related pathways, and whether endogenous changes in stress hormones following an aversive experience modulate memory strength, precision, or both.  

A Novel Approach for Elucidating the Neural Mechanisms of Stress Resilience  

Stress inoculation is a form of cognitive behavioral therapy involving intermittent exposure to mild stressors for people in occupations that involve exposure to life-threatening situations, such as in the military, firefighting, and law enforcement. Stress inoculation in humans may be used to reduce adverse reactions to stress, and it shares some features with exposure therapy. In conjunction with our colleague Dr. Sarah Ayash (Johannes Guttenberg University Mainz), we have developed a stress inoculation regimen in rats that promotes the same traits found in stress resilient humans, such as better situational coping and adaptation to subsequent stressful experiences. In this line of inquiry, our current work involves validating additional behavioral features of inoculation in male and female rats that are homologous to human resilience. In the next stage, we aim to identify the key changes in brain pathways that drive the effects of stress inoculation. Our long-term goal is to reveal a novel circuit mechanism that could inform the future prevention or alleviation of stress related psychiatric diseases, such as depression, anxiety, and PTSD.