Neurophysiological mechanisms of Stress Coping Behaviors

压力应对行为的神经生理机制

• 批准号: 9278487
• 负责人: Allyson Kimberly Friedman
• 金额: $ 15.6万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9278487
• 关键词: Animal Model; Anterior; Anxiety; Arousal; Award; Behavior; Behavioral; Behavioral Model; Brain; Brain region; Cities; Clinical; Coping Behavior; Coping Skills; Data; Depressive disorder; Development; Diagnosis; Disease; Dopamine; Dopaminergic Cell; Electrophysiology (science); Evaluation; Event; Exhibits; Expectancy; Female; Foundations; Functional disorder; Gender; Genes; Glutamates; Goals; Grant; Health; Human; Incidence; Individual; Individual Differences; Interneurons; Lead; Life; Light; Link; Maintenance; Major Depressive Disorder; Mediating; Mental Depression; Mentors; Mentorship; Modeling; Motivation; Mus; National Institute of Mental Health; Nature; Neurobiology; Neurons; New York; Pathologic; Pathway interactions; Pharmacology; Phenotype; Pilot Projects; Play; Population; Positioning Attribute; Predisposition; Property; Publications; Research; Research Support; Resistance; Rewards; Role; Running; Series; Social Behavior; Societies; Stimulus; Stress; Stress and Coping; Structure of terminal stria nuclei of preoptic region; Techniques; Testing; Therapeutic; United States National Institutes of Health; Universities; Variant; Ventral Tegmental Area; Viral; Work; avoidance behavior; behavioral response; behavioral study; biological adaptation to stress; career; cell type; college; coping; coping mechanism; depressive symptoms; design; dopaminergic neuron; experience; gender difference; gender disparity; insight; male; mental function; neural circuit; neuroadaptation; neurobiological mechanism; neuronal excitability; neurophysiology; neuropsychiatric disorder; novel; programs; resilience; response; reward circuitry; sex; social; social stress; stressor; targeted treatment; therapy development; translational study

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.

摘要 对社会压力的行为反应有很大的差异。有些人成功地运用应对 应对压力的策略，并变得有弹性。在其他情况下，社会压力会导致精神疾病 功能障碍，如抑郁和焦虑。虽然应对机制是众所周知的关键， 保持健康的心理功能和适当的，成功的应对策略， 压力和保护从长期的病理状态，有较少的了解神经生理学基础 这是如何发生的。重要的是，临床上很明显，易受压力诱导的神经精神疾病 疾病是高度个体化的，可能部分取决于这些应对方式。人类研究表明， 在压力性生活事件中的应对与压力诱发的抑郁症的发展相关，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，表明可能发生的非重叠神经回路适应反应， 应力尽管有这些明显的性别差异和女性抑郁症发病率的增加， 这一领域的翻译工作主要侧重于男性。识别神经生物学性别差异 在压力应对反应中，可以为抑郁症提供急需的机械驱动疗法。的 该奖项中提出的动物模型将提供对压力的关键机制和神经回路理解 应对策略对应激反应有影响。对压力引起的疾病的脆弱性是高度个体化的 并且可能部分取决于可变的应对方式。在反复的压力下，会有更多的兴奋， 期望和焦虑。正是这些功能促进了电路水平的应对，因此我们的工作重点是 在那些相关的大脑区域。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，BNST项目和规范射击 多巴胺能细胞通过腹侧被盖区（VTA）内的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BNST神经元是唯一的 被定位为接收压力轴信息并将其整合到奖励/激励电路中。的两个具体 该提案概述的目标将充分描述这些行为模型， BNST-VTA通路内发生的变化研究导致进一步了解 积极压力应对策略的神经生理机制，以及它们如何增强对压力的抵抗力。 压力诱发的抑郁症可能提供新的药理学靶点，以提高应对技能和逆转 抑郁症状总括而言，本研究计划所建议的研究， 奖学金（SC2）对我的独立研究道路的发展至关重要。这种机制将提供 我在纽约城市大学亨特学院的职业生涯的下一步， 约克。