Neural circuit mechanisms for experience-dependent observational fear

项目总结 在一种情况下替代地体验对方的厌恶情绪的能力，这一过程称为观察性 恐惧对于生活在社会中是至关重要的。OF的功能障碍代表着患者的良好表现 自闭症谱系障碍。在Of中，一名观察员目睹了一名处于厌恶状态的示威者，并 以恐惧行为回应。如果示威者的反应强烈，观察者很容易表达出 没有类似的经验和对示威者的社会熟悉度(我们称之为先天的)。然而， 在自然界和我们的生活中，示威者的反应往往是模棱两可的，因此观察者很难 理解。为了充分了解对方的情况，观察者利用两人之前类似的自己的经验 和促进的社会熟悉度(我们称之为经验依赖的；经验依赖的)。与生俱来的 主要依赖于前扣带回皮质(ACC)和基底外侧杏仁核(BLA)这两个神经 Exp的作用机制尚不清楚。我的目标是阐明前两者的神经机制 相似的亲身经历和社会熟悉度使观察者能够充分理解对方的反感 通过检查小鼠的海马(HPC)-BLA神经回路，从他们的模糊反应中观察情况 向演示者发出强烈电击以引发强烈反应或微弱电击的模型 引发模棱两可的反应的震惊。 最近，我们的初步研究表明，ACC对于Exp是可有可无的，而ACC是必不可少的 与生俱来的。另一方面，背侧HPC(DHPC)和腹侧HPC(VHPC)都是Exp的关键， 但不是与生俱来的。BLA对于Exp和Inside Of都是必需的。这些发现使我们提出了截然不同的 神经回路在经验和先天的。该模型的中心假设是背腹侧HPC至BLA 通路产生并重新激活编码先前类似的自身恐惧的BLA神经元的神经集合 以Strong为指导 初步数据，首先，我们认为背腹侧HPC到BLA的通路是Exp的关键，而 ACC到BLA途径是先天性骨质疏松症所必需的。第二，我们认为神经的重新激活 编码先前类似自身恐惧体验的BLA神经元集合(恐惧记忆集合)起中介作用 作为感知-行动机制的实验。第三，我们提出了从dHPC到BLA的途径 在自己的恐惧体验过程中，在BLA中产生恐惧记忆集合，然后vHPC神经元对 熟悉示威者的恐惧情境重新激活了BLA中的恐惧记忆集合以引发实验。 经验，这促进了Exp，而ACC诱导了天生的BLA活性。 总的来说，我们提出的研究将通过以下方式广泛影响学习和记忆领域 描述我们如何理解对方的厌恶情绪的神经回路及其神经过程 情景体验。潜在地，神经机制可以推广到其他类型的移情 替代地体验他人的感受/处境。

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.