Impact of social drive on social fear learning and amygdala function during development

社会驱力对发育过程中的社交恐惧学习和杏仁核功能的影响

• 批准号: 10020193
• 负责人: Nicole Christine Ferrara
• 金额: $ 6.53万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2022-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10020193
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Affect; Age; Amygdaloid structure; Anterior; Anxiety Disorders; Behavior; Behavioral; Biological; Brain; Cells; Child; Data; Development; Diagnosis; Disadvantaged; Disease; Electrophysiology (science); Extinction (Psychology); Freezing; Fright; Glutamates; Goals; Individual; Intervention; Investigation; Lead; Learning; Longevity; Measures; Memory; Modeling; Modification; Pathology; Pathway interactions; Performance; Population; Post-Traumatic Stress Disorders; Predisposition; Procedures; Process; Readiness; Recurrence; Resistance; Risk; Rodent; Role; Social Behavior; Social Functioning; Social Interaction; Social isolation; Source; Symptoms; Synapses; Testing; Therapeutic Intervention; Trauma; age related; base; cingulate cortex; conditioned fear; conditioning; disabling symptom; experience; experimental study; fear memory; high risk; memory encoding; memory recall; neuromechanism; novel therapeutic intervention; optogenetics; receptor expression; response; social; social deficits; social learning; stress related disorder; targeted treatment; traumatic event; vulnerable adolescent

PROJECT ABSTRACT Heightened fear responding and social dysfunction are commonly seen in individuals suffering from debilitating fear-related disorders, such as Post-Traumatic Stress Disorder (PTSD). Exposure-based treatments are often ineffective at minimizing robust fear responses. Adolescents are especially prone to the development of fear- and stress-related disorders as well as symptom persistence following therapeutic interventions. Understanding developmental differences in the persistence of fear could therefore lead to more targeted, age-appropriate interventions. Directly experienced traumatic events are significant triggers in anxiety disorders and PTSD. However, adolescent observation of trauma or abuse also increases risk of diagnosis. The impact of observed trauma depends on the social sensitivity of the observer, which is high during adolescence. This social sensitivity combined with ongoing brain maturation may produce adolescent vulnerabilities for these disorders. The investigation of factors that contribute to behavioral and biological changes across the lifespan is critical for a thorough understanding of adaptive fear responding. The goal of this proposal is to identify the factors that contribute to socially learned fear in adults and adolescents, and how these factors lead to persistent fear behavior during adolescence. We will use social fear learning (SFL), which requires social interaction and social inference, and requires amygdala circuits to learn and retain fear. We hypothesize that changes in social sensitivity and amygdala circuitry from adolescence to adulthood contribute to differences in how SFL is learned and retained. We will test this general hypothesis in two specific aims. Aim 1 will determine how changes in social drive between adults and adolescents impact SFL and retention as well as cortico-amygdala synaptic strength using whole cell electrophysiology. Aim 2 will target how socially-inferred fear responding may change with acute manipulations in observed fear using optogenetics, and the impact this has on synaptic strength in the amygdala using whole cell electrophysiology. These results will provide information for new therapeutic strategies to understand the developmental differences in how fear is retained through changes in social drive.

项目摘要 恐惧反应增强和社交功能障碍通常见于患有衰弱性痴呆的个体。 与恐惧有关的疾病，如创伤后应激障碍（PTSD）。基于暴露的治疗通常 在最大限度地减少强烈的恐惧反应方面无效。青少年特别容易产生恐惧- 和压力相关的疾病以及治疗干预后的症状持续性。理解 因此，恐惧持续性的发展差异可能会导致更有针对性的，适合年龄的 干预措施。直接经历的创伤性事件是焦虑症和PTSD的重要触发因素。 然而，青少年对创伤或虐待的观察也增加了诊断的风险。观察到的影响 创伤取决于观察者的社会敏感性，这种敏感性在青少年时期很高。这种社会敏感性 再加上正在进行的大脑成熟可能会导致青少年对这些疾病的脆弱性。的 对导致整个生命周期行为和生物变化的因素的调查对于一个 深入了解适应性恐惧反应。本提案的目标是确定 有助于成年人和青少年的社会学习恐惧，以及这些因素如何导致持续的恐惧 青春期的行为。我们将使用社会恐惧学习（SFL），这需要社会互动和社会 这需要杏仁核回路来学习和保持恐惧。我们假设社会的变化 从青春期到成年期的敏感性和杏仁核回路有助于SFL学习方式的差异 并保留。我们将在两个具体目标中检验这个一般假设。目标1将决定 成人与青少年社会内驱力对SFL和记忆保持以及皮质-杏仁核突触影响 使用全细胞电生理学的力量。目标2将针对社会推断的恐惧反应可能如何变化 使用光遗传学观察到的恐惧中的急性操纵，以及这对突触强度的影响， 杏仁核的全细胞电生理学。这些结果将为新的治疗方法提供信息。 策略，以了解如何通过社会驱动力的变化保持恐惧的发展差异。