Neurobiology of Social Behavior

社会行为神经生物学

• 批准号: 9040789
• 负责人: KIM L HUHMAN
• 金额: $ 37万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9040789
• 关键词: Adopted; Aggressive behavior; Agonist; Amygdaloid structure; Animals; Anxiety; Anxiety Disorders; Area; Behavior; Behavioral; Brain; Brain region; Brain-Derived Neurotrophic Factor; Code; Conflict (Psychology); Data; Development; Disease; Drug abuse; Employee Strikes; Epigenetic Process; Exons; Exposure to; Figs - dietary; Future; Genes; Goals; Hamsters; Health; Hippocampus (Brain); Histone Acetylation; Histone Deacetylase Inhibitor; Histone Deacetylation; Human; Individual; Informatin; Investigation; Learning; Literature; Mediating; Mediator of activation protein; Mental Depression; Mental disorders; Messenger RNA; Microinjections; Modeling; Molecular; Mood Disorders; Neurobiology; Nucleus Accumbens; Patients; Pattern; Pharmaceutical Preparations; Physiological; Post-Traumatic Stress Disorders; Prevalence; Protein Tyrosine Kinase; Risk Factors; Signal Transduction; Site; Social Behavior; Stress; Symptoms; System; Testing; Work; base; behavioral response; chromatin remodeling; depressive symptoms; drug development; histone methylation; improved; mood regulation; neural circuit; neuromechanism; neurotrophic factor; noradrenergic; prevent; promoter; public health relevance; receptor; resilience; response; small molecule; social; social stress; stem; treatment strategy

DESCRIPTION (provided by applicant): Exposure to social stress has pervasive deleterious effects on health and is a primary risk factor for the development of depression and anxiety disorders. Despite the prevalence of these disorders, our current treatment strategies are woefully inadequate. One of the fundamental reasons that we have not developed better treatments is that these so-called pathological states likely stem from evolutionarily adaptive behavioral patterns that are adopted when individuals perceive social stress or defeat. This would help explain not only their prevalence but also their persistence. In many non-human species exposure to social stress also causes persistent physiological and behavioral responses that closely mimic the symptoms of depression and PTSD. What is desperately needed is an understanding of how social stress shifts behavior from one stable state to another. My lab has developed an ethologically relevant model in hamsters termed conditioned defeat (CD), wherein even a single exposure to social defeat stress causes a striking behavioral shift from social engagement and aggression to social avoidance and submission. The ultimate goal of our work is to delineate the neural mechanisms of such stress-induced shifts in behavioral state and to discover how these changes might be prevented or reversed. This project will test the overarching hypothesis that brain derived neurotrophic factor (BDNF) systems within specific regions of the CD neural circuit mediate, at least in part, behavioral changes observed following social defeat stress. We propose that BDNF can both promote and prevent these changes depending on the brain area involved (Aim 1) and that these actions are mediated by BDNF actions on tyrosine kinase B (TrkB) receptors (Aim 2). We also propose that chromatin remodeling of the BDNF gene and promoters is a molecular mechanism underlying the behavioral changes that define CD (Aim 3). In this project, we will not only delineate the site specific behavioral effects of, and defeat-induced epigenetic changes in, the BDNF-TrkB system in the neural circuit for CD, but we will also assess the translational potential of this informatin with systemic manipulations. Advancing our understanding of the mechanisms involved in shifts among stable behavioral states will dramatically advance our ability to treat intractable mood and anxiety disorders such as depression and PTSD.

描述（由申请人提供）：暴露于社会压力对健康有害影响，是抑郁症和焦虑症的发展的主要危险因素。尽管这些疾病的普遍性，但我们当前的治疗策略却不足。我们没有开发更好治疗方法的基本原因之一是，这些所谓的病理状态可能源于当个人意识到社会压力或失败时所采用的进化适应性行为模式。这将不仅有助于解释他们的盛行，而且有助于他们的持久性。在许多非人类物种中，暴露于社会压力也会导致持续的生理和行为反应，这些反应紧密模仿了抑郁症和PTSD的症状。迫切需要的是了解社会压力如何将行为从一个稳定状态转移到另一个稳定状态。我的实验室已经在被称为条件失败的仓鼠（CD）中开发了一种与伦理学相关的模型，即使是一次接触社会失败压力，也会导致从社会参与和侵略到社会回避和提交的行为转变。我们工作的最终目标是描述这种压力引起的行为状态转变的神经机制，并发现如何预防或逆转这些变化。该项目将检验以下总体假设，即CD神经回路介导的特定区域内的脑衍生神经营养因子（BDNF）系统，至少部分部分是社交失败压力后观察到的行为变化。我们建议BDNF既可以根据所涉及的大脑区域（AIM 1）促进和预防这些变化（AIM 1），并且这些作用是由BDNF对酪氨酸激酶B（TRKB）受体（AIM 2）的作用介导的。我们还建议BDNF基因的染色质重塑，启动子是一种分子机制，其行为变化定义CD的行为变化（AIM 3）。在这个项目中，我们不仅会描述网站 CD的神经回路中BDNF-TRKB系统的特定行为影响和失败诱导的表观遗传变化，但我们还将通过全身性操纵来评估该信息素的翻译潜力。促进我们对稳定行为状态中涉及的机制的理解将极大地提高我们治疗顽固性情绪和焦虑症（如抑郁症和PTSD）的能力。