Neurophysiological basis of experience influence in observational fear

摘要 人类和动物可以感知和回应他人令人厌恶的经历，这是一种对同理心至关重要的能力， 社会纽带，对生存很重要。在这里，我们研究大脑中的神经回路如何产生观察性信息 恐惧，一个受试者对处于恐惧中的另一个受试者的观察表现出恐惧的反应。 之前的行为和人体成像研究已经揭示了先前厌恶的强大影响 对这一行为的经验，也发现了几个涉及的大脑区域。然而，是什么神经元 活体中的活动模式允许一个受试者主观地将其他人的经历视为厌恶的残余物 很神秘。鉴于先前经验对观察性恐惧的强烈影响，我们提出了一个假设 观察时的主观恐惧感由前扣带回皮质(ACC)的神经元代表， 但强烈地受到海马体(HP)中一种特殊的神经元活动模式的影响，这种模式称为觉醒重播， 这让人回想起之前的可怕经历。我们将通过同时记录大量数据来检验这一假设 在观察恐惧任务中，大鼠ACC和HP中单个神经元的数量。我们将首先确定惠普如何唤醒 重播和相关的ACC活动模式与观察到的恐惧的行为测量相关 以及它们是如何在HP和ACC神经回路中产生的。第二，我们将确定关键因素如何 与先前的经验相关，调节作为观察性恐惧基础的ACC/HP活动模式。特别是， 我们将研究先前经验的新近性、效价、空间和社会背景的影响。最后，我们会 通过干扰Acc/HP活动模式与观察到的恐惧之间的因果关系 然后考察其对行为测量的影响。这项研究的结果将显著地 加深我们对观察恐惧中神经回路计算的理解，并可能揭示出 通过回忆先前的恐惧经历，了解它如何产生的活体神经机制。这项研究可能会打开 了解精神障碍的反社会症状的大门，如反社会人格障碍和 精神分裂症，并可能启发新的治疗策略。 1

Abstract Humans and animals can sense and respond to aversive experiences of others, an ability crucial for empathy, social bonding and important for survival. Here we study how neural circuits in the brain produce observational fear, a behavior of one subject displaying fearful responses to the observation of another subject in fear. Previous behavioral and human imaging studies have revealed a powerful influence of prior aversive experience on this behavior and have also identified several brain areas involved. However, what neuronal activity patterns in vivo allow one subject to subjectively perceive the others’ experiences as aversive remains mysterious. Given the strong influence of prior experience on observational fear, we propose a hypothesis that the subjective sense of fear upon observation is represented by neurons in the anterior cingulate cortex (ACC), but strongly influenced by a particular neuronal activity pattern in the hippocampus (HP), called awake replay, that recalls prior fearful experiences. We will test the hypothesis by simultaneous recording of a large number of single neurons in ACC and HP in rats during observational fear tasks. We will first determine how HP awake replay and the associated ACC activity patterns are correlated with behavioral measures of observational fear and how they are generated within the HP and ACC neural circuits. Second, we will determine how key factors related to prior experience modulate the ACC/HP activity patterns underlying observational fear. In particular, we will study the effects of recency, valence, spatial and social contexts of prior experience. Finally, we will determine how the ACC/HP activity patterns are causally related to observational fear by disrupting these patterns and then examining its impacts on behavioral measures. The outcomes of this study will significantly advance our understanding of neural circuit computations in observational fear and may reveal a specific in vivo neural mechanism of how it can be produced by recalling prior fearful experiences. This study may open the door to understand antisocial symptoms in mental disorders such as antisocial personality disorder and schizophrenia and may inspire novel therapeutic strategies. 1