Neural circuit mechanisms for experience-dependent observational fear

经验依赖性观察恐惧的神经回路机制

• 批准号: 10675103
• 负责人: Takashi Kitamura
• 金额: $ 46.98万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-07 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10675103
• 关键词: Amygdaloid structure; Anterior; Behavior; Cells; Communication; Data; Dorsal; Empathy; Familiarity; Feeling; Fright; Gene Expression; Generations; Genetic; Goals; Hippocampus; Immediate-Early Genes; Mediating; Memory; Modeling; Mus; Nature; Neural Pathways; Neurons; Pathway interactions; Perception; Population; Process; Reaction; Research; Role; Shock; Societies; Testing; cingulate cortex; experience; fear memory; field study; in vivo calcium imaging; individuals with autism spectrum disorder; neural; neural circuit; neuromechanism; social

PROJECT SUMMARY The ability to vicariously experience the other's aversive feelings in a situation, a process called observational fear (OF), is critical to live in society. Malfunctions of OF represent well-described findings in individuals with autism spectrum disorders. In OF, an observer witnesses a demonstrator in an aversive situation and responds with fear behaviors. If the demonstrator's reaction is robust, the observer easily expresses OF without prior similar experience and social familiarity with demonstrator (we refer to as innate OF). However, in nature and our lives, the demonstrator's reaction is often ambiguous and thus difficult for the observer to understand. To fully understand the other's situation, the observer utilizes both prior similar own experience and social familiarity that facilitate OF (we refer to as experience-dependent OF; Exp OF). While innate OF primarily depends on the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), the neural mechanisms of Exp OF remain unexplored. My goal is to elucidate the neural mechanisms of how both prior similar own experience and social familiarity enable the observer to fully understand the other's aversive situation from their ambiguous reaction, by examining hippocampal (HPC)-BLA neural circuits in a mouse OF model that delivers strong electrical shocks to the demonstrator eliciting a robust reaction or weak electrical shocks eliciting an ambiguous reaction. Recently, our preliminary studies showed that ACC is dispensable for Exp OF, while ACC is essential for innate OF. On the other hand, both dorsal HPC (dHPC) and ventral HPC (vHPC) are crucial for Exp OF, but not for innate OF. BLA is required for both Exp and innate OF. These findings lead us to propose distinct neural circuits in Exp and innate OF. The central hypothesis of this model is that the dorsoventral HPC to BLA pathways generate and reactivate a neural ensemble of BLA neurons encoding prior similar own fear Guided by strong preliminary data, first, we propose that the dorsoventral HPC to BLA pathways are crucial for Exp OF, while the ACC to BLA pathway is essential for innate OF. Second, we propose that the reactivation of a neural ensemble of BLA neurons encoding prior similar own fear experience (a fear memory ensemble) mediates Exp OF as the perception-action mechanisms. Third, we propose that the pathway from dHPC to BLA generates the fear memory ensemble in BLA during own fear experience and then vHPC neurons respond to the familiar demonstrator's fearful situation to reactivate the fear memory ensemble in BLA to elicit Exp OF. experience, which facilitates Exp OF, while ACC induces robust BLA activity for innate OF. Collectively, our proposed research will broadly impact the field of learning and memory by characterizing neural circuits and their neural process about how we understand the other's aversive situational experience. Potentially, the neural mechanisms can be generalized for other types of empathy to vicariously experience the other's feeling/situation.

项目摘要 在一种情况下间接体验他人厌恶情绪的能力，这一过程称为观察 恐惧（OF），是生活在社会中的关键。OF的功能障碍代表了在患有以下疾病的个体中的良好描述的结果： 自闭症谱系障碍。在OF中，一个观察者目睹了一个示威者在一个令人厌恶的情况下， 表现出恐惧的行为如果演示者的反应是鲁棒的，观察者很容易表达OF 没有先前的类似经验和与演示者的社会熟悉度（我们称之为先天的OF）。然而，在这方面， 在自然界和我们的生活中，演示者的反应往往是模棱两可的，因此观察者很难 明白为了充分了解对方的情况，观察者利用双方先前相似的自身经验 和社会熟悉度，促进OF（我们称之为经验依赖的OF; Exp OF）。虽然先天的 主要取决于前扣带皮层（ACC）和基底外侧杏仁核（BLA），神经系统的 Exp OF的机制尚未探索。我的目标是阐明神经机制， 相似的自身经历和社会熟悉度使观察者能够充分理解对方的厌恶 从他们的模糊反应的情况下，通过检查海马（HPC）-BLA神经回路在一个小鼠OF 一个模型，提供强大的电击，以演示引发强大的反应或弱电 引起不明确反应的冲击。 近年来，我们的初步研究表明，ACC是Exp OF的重要组成部分，而ACC是必需的， 先天的。另一方面，背侧HPC（dHPC）和腹侧HPC（vHPC）对于Exp OF都是至关重要的， 但不是先天的。BLA是Exp和先天OF所必需的。这些发现使我们提出了不同的 神经回路的经验和先天的。该模型的中心假设是，背腹HPC到BLA 通路产生并重新激活BLA神经元的神经系综， 以强为导 初步数据，首先，我们提出背腹侧HPC到BLA通路对Exp OF至关重要， ACC到BLA通路是先天性OF所必需。第二，我们提出，神经元的重新激活 BLA神经元的集合编码先前类似的自身恐惧体验（恐惧记忆集合）介导 理解-行动机制。第三，我们认为，从dHPC到BLA的途径 在自己的恐惧体验期间在BLA中产生恐惧记忆集合，然后vHPC神经元做出反应 熟悉的演示者的恐惧情境，重新激活BLA中的恐惧记忆集合，引出Exp OF。 经验，这有利于Exp OF，而ACC诱导强大的BLA活动先天OF。 总的来说，我们提出的研究将广泛影响学习和记忆领域， 描述我们如何理解对方的厌恶的神经回路和神经过程 情境体验潜在地，神经机制可以推广到其他类型的同理心， 间接地体验别人的感受/处境。