Neurophysiological mechanisms of Stress Coping Behaviors

摘要 对社会压力的行为反应有很大的不同。一些人成功地使用了应对 应对压力的策略，并变得有弹性。在另一些国家，社会压力可能会导致精神疾病 功能障碍，如抑郁和焦虑。虽然众所周知，应对机制对 保持健康的心理功能和适当、成功的应对策略可以减少 应激和保护免受长期病理状态的影响，其神经生理学基础知之甚少 这是如何发生的。重要的是，临床上很明显，易受应激诱导的神经精神障碍 疾病是高度个体化的，可能在一定程度上取决于这些应对方式。人体研究表明，被动的 在有压力的生活事件中的应对方式与压力诱导的抑郁的发展有关，而 积极应对与复原力相关。有趣的是，男性和女性表现出不同的社会压力 应对策略，暗示潜在的非重叠神经回路适应发生在对 压力。尽管存在这些明显的性别差异，女性严重抑郁症的发生率也有所增加， 这一领域的翻译工作主要集中在男性身上。识别神经生物学的性别差异 在压力应对反应中，可能会提供急需的机械驱动的抑郁症治疗方法。这个 该奖项中提出的动物模型将提供对应激的重要机制和神经回路的理解。 应对策略对应激反应有影响。对应激性疾病的易感性是高度个人化的 而且可能在一定程度上取决于不同的应对方式。在反复的压力之后，会有更多的唤醒， 期望和焦虑。正是这些功能促进了电路级别的应对，因此我们的工作重点 在这些相关的大脑区域。最近的研究揭示了前床的关键和相反的作用 终纹核(BNST)。此外，英国国家安全局计划和管理射击 腹侧被盖区(VTA)内的多巴胺能细胞通过GABA能中间神经元，该区域已被 显示与压力相关的抑郁表型有关。因此，VTA投射的BNST神经元是独特的 定位为接收压力轴信息，并将其整合到奖励/激励电路中。这两个具体的 这项提案概述的目标将充分描述这些行为模型并确定神经生理学 BNST-VTA通路研究中发生的变化导致对 积极应激应对策略的神经生理学机制以及它们如何增强对 应激引起的抑郁可能提供新的药物靶点来提高应对技能和逆转 抑郁症状。综上所述，本研究提出的支持竞争性研究先导项目 获奖(SC2)对我的独立研究道路的发展至关重要。这一机制将提供 为我在纽约城市大学亨特学院的下一步职业生涯提供财务和指导支持 约克市。

Abstract 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.