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

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的个体 与恐惧相关的障碍，如创伤后应激障碍(PTSD)。基于暴露的治疗通常是 在最大限度地减少强烈恐惧反应方面效果不佳。青少年尤其容易产生恐惧情绪-- 与压力相关的障碍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、更适合年龄的人 干预措施。直接经历的创伤事件是焦虑症和创伤后应激障碍的重要触发因素。 然而，青少年对创伤或虐待的观察也会增加诊断的风险。观察到的影响 创伤取决于观察者的社会敏感度，这种敏感度在青春期很高。这种社会敏感性 再加上正在进行的大脑成熟，可能会产生青少年对这些疾病的脆弱性。这个 对导致人一生中行为和生物变化的因素进行调查对于 对适应性恐惧反应的透彻理解。这项提案的目标是确定以下因素 有助于成人和青少年的社交习得恐惧，以及这些因素是如何导致持续恐惧的 青春期的行为。我们将使用社交恐惧学习(SFL)，这需要社交互动和社交 推理，并需要杏仁核回路来学习和保持恐惧。我们假设社会上的变化 从青春期到成年期的敏感度和杏仁核回路导致了SFL学习方式的不同 并予以保留。我们将在两个具体目标上检验这一普遍假设。目标1将决定如何改变 成人和青少年之间的社会动机影响SFL和保留以及皮质-杏仁核突触 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发生的变化 利用光遗传学在观察到的恐惧中进行急性操纵，以及这对突触强度的影响 杏仁核使用全细胞电生理学。这些结果将为新的治疗方法提供信息 了解恐惧如何通过社会驱动力的变化保留的发展差异的策略。

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.