疼痛共情的实验动物模型及其神经环路研究

Empathy, a basic prosocial behavior, is referred to as an ability to understand and share other’s emotional state. Empathy is also a basis of altruism. In contrast, anti-empathy may be associated with autism, narcissism, alexithymia, personalality disorders, schizophrenia and depression. Thus study of the brain mechanisms of empathy has great importance to both scientific and clinical advances. However, less is known about the molecular and cellular mechanisms of empathy due to lack of laboratory animal models in that only human and non-human primates have been considered to have such unique emotional sharing. Recently, a group from McGill university and we independently found that both mice and rats have empathy for pain. We also mapped out that the medial prefrontal cortex including the anterior cingulate cortex, prelimbic cortex and infralimbic cortex is involved in pain empathy in rats, suggesting existence of a neural network associated with development of pain empathy in the CNS. In the present project, bio-psychosocial-behavioral model and converging techniques including optogenetics, in vivo multi-site and multi-electrode array recording, in vitro brain slice multi-electrode array recording, brain slice-patchclamp recording, molecular and cellular neurobiological approaches will be used to unravel the neural circuitry of pain empathy so as to provide a model system for studying the brain mechanisms of empathy and its related diseases.

共情是最基本的亲社会行为，是一种理解和分享别人情绪状态和感受的能力，是同甘苦共患难利他主义思想形成的基础。反之，共情障碍可能与自闭症、自恋症、情述障碍、人格障碍、精神分裂症和抑郁症发生相关，因此研究共情发生的脑机制既有科学意义，更有临床意义。然而由于认为只有人类和非人灵长类才独有共情，所以长期导致实验动物模型缺如，致使缺乏对其分子与细胞机制的了解。近年，加拿大麦吉尔大学和我们研究组分别独立地发现小鼠和大鼠均具有疼痛共情反应。此外，我们还发现内侧前额叶（包括ACC、前边缘皮质、下边缘皮质）参与大鼠的疼痛共情反应，提示中枢神经系统内存在一个与疼痛共情有关的神经环路。本项目将在生物-社会心理-行为模型的框架下，集成多种技术如光遗传学、在体多部位多电极阵列记录技术、离体脑片微电极阵列记录技术、脑片膜片钳记录和分子与细胞神经生物学方法解析疼痛共情的神经环路，为研究共情及其相关疾病的脑机制提供模型系统

本项目按计划基本完成两方面内容，其一是构建、优化和完善大小鼠实验动物疼痛共情模型和研究范式，在低等啮齿类动物至少鉴定出初中级两类共情反应：①共情性观获疼痛传染（Empathic observational contagious pain, EOCP）；②共情安抚（Empathic consolation, EC）和靶向特异的帮助行为（Targeted help），提出和验证了评估EOCP和EC的行为学参数和定性定量标准。研究了疼痛共情的大小鼠种属和性别特征，确定了种属同一性和小鼠性别差异性。其二，应用该模型探索并证明了高度保守的中枢神经系统与外周促亲社会激素和化学物质如去甲肾上腺素、5-HT、催产素、加压素、雌激素等在促进共情发生中的正性调节作用以及下丘脑-垂体-肾上腺皮质激素在压抑共情发生中的负性调节作用。利用现代分子与细胞神经生物学技术揭示了来自于下丘脑室旁核的催产素和来自于脑干中缝核群的5-HT通过作用于内侧前额叶的受体驱动大鼠疼痛共情行为的分子和神经机制，为“俄罗斯套娃”共情进化学说提供了生物学基础。最后，本项目还拓展了共情的概念和理论学说，为开辟共情神经科学新领域提出发展设想。