There are wide variations in behavioral responses to social stress. Some individuals successfully employ coping strategies in response to stress, and become resilient. In others, social stress can precipitate psychiatric dysfunction, such as depression and anxiety. While coping mechanisms are known to be crucial for the maintenance of healthy mental functioning and a proper, successful coping strategy decreases the impact of stress and protects from long-term pathological states, there is less known about the neurophysiological basis of how this occurs. Importantly, it is clinically evident that vulnerability to stress-induced neuropsychiatric diseases is highly individual and may in part depend on these coping style. Human studies suggest that passive coping during stressful life events is associated with the development of stress-induced depression, whereas proactive coping is correlated with resiliency. Interestingly, males and females demonstrate different social stress coping strategies, suggesting potentially non-overlapping neural circuitry adaptations occurring in response to stress. Despite these clear gender differences and the increased incidence of major depression in females, translational work in this field has focused primarily on males. Identifying the neurobiological gender differences in stress coping responses may inform greatly needed mechanistically driven therapeutics for depression. The animal models proposed in this award will provide crucial mechanistic and neural circuit understanding of stress coping strategies influence on the stress response. Vulnerability to stress-induced diseases is highly individual and may in part depend on variable coping styles. Following repeated stress, there is increased arousal, expectancy and anxiety. It is these functions that facilitate coping at the circuit level, therefore our work focuses on those related brain regions. Recent studies have revealed the critical and opposing roles of the anterior bed nucleus of the stria terminalis (BNST). Furthermore, the BNST projects to and regulates the firing of dopaminergic cells via GABAergic interneurons within the ventral tegmental area (VTA), a region which has been shown to be linked to stress-related depressive phenotype. Thus the VTA projecting BNST neurons are uniquely positioned to receive stress axis information and integrate it into reward/motivation circuitry. The two specific aims outlined this proposal will fully characterize these behavioral models and identify neurophysiological changes that occur within the BNST-VTA pathway Research leading towards further understanding of the neurophysiological mechanisms of active stress coping strategies, and how they can enhance resistance to stress induced depression may provide novel pharmacological targets to enhance coping skills and reverse depressive symptoms. In summary, the research proposed in this Support of Competitive Research Pilot Project Award (SC2) is critical for the development of my independent research path. This mechanism will provide the financial, and mentorship support for the next steps in my career at Hunter College at the City University of New York.
statement Stress induced depression has a tremendous negative impact on the health of the individual and society. The research generated in this proposal will investigate a discrete neural circuit that mediates differential responses to stress, dependent on sex and coping strategy. These data will shed light on the neurobiological mechanisms underlying the differences in stress response in males and females and may lead to the development of potential targeted therapeutics to treat depression.
| Juarez, Barbara; Morel, Carole; Ku, Stacy M et al. (2018) Author Correction: Midbrain circuit regulation of individual alcohol drinking behaviors in mice. Nat Commun 9:653 |
| Juarez, Barbara; Morel, Carole; Ku, Stacy M et al. (2017) Midbrain circuit regulation of individual alcohol drinking behaviors in mice. Nat Commun 8:2220 |
