The Neurobiology of Social Response to Distress

同理心，或检测和回应他人情绪的能力，是正常社会沟通的基本组成部分，也是维持社会关系所必需的。许多社会认知障碍，包括自闭症谱系障碍，精神分裂症和精神病，其特征是共情缺陷，这会损害正常的社会互动并降低生活质量。尽管如此，人们对共情的生物学机制知之甚少，也没有治疗这些缺陷的医学干预措施。在开发这种医学疗法之前，我们必须解决我们对共情生物学知识的重大缺口。最近的各种研究表明，许多动物也有能力检测和回应其他动物的情绪。因此，这种知识上的差距可以而且应该通过使用适当的动物模型来解决，这些动物模型显示出类似于人类行为的基于同理心的行为。人类对他人的痛苦的一种常见的基于同情的反应是提供安慰。现在已知，对他人痛苦的社会反应存在于少数动物物种中，这使其成为了解更多关于共情生物学的理想候选行为。我们的实验室已经证明了第一次，实验室啮齿动物，草原田鼠，显示在实验条件下的痛苦的社会反应，这种行为是基于移情，并通过管理的催产素（OT）受体拮抗剂直接进入大脑的行为被废除。因此，我们的实验室处于独特的位置，以一种在任何其他现有模型中都不可能的方式发现对痛苦的社会反应的神经生物学基础。我们建议使用草原田鼠对痛苦的社会反应作为学习共情神经生物学的模型。为了了解这些知识，我们提出了以下具体实验。在目标1中，我们提出定位一个或多个特定的脑区，其中OT受体拮抗剂起作用，以防止安慰。我们将使用特定部位的拮抗剂输注结合我们的试点研究中开发的社会困扰测试来实现这一目标。在目标2中，我们将通过定位OT释放到感兴趣区域的来源来扩展这个神经回路。我们将使用三重标记技术来定位包含OT的神经元，投射到感兴趣的区域，并在对痛苦的社会反应中活跃。在目标3中，我们建议确定在发育过程中OT受体密度的自然变化如何影响安慰。为了确定这一点，我们将实验操作的OT受体的密度在青少年草原田鼠使用病毒载体技术在我们的实验室开发，并测量这些操作在成年后的社会反应的痛苦的影响。这些实验的结果将开始弥合我们对共情知识的差距，提供草原田鼠对痛苦的社会反应的行为回路的第一个证据。拟议的实验将扩大我们的社会认知和痛苦的社会反应的神经生物学知识。此外，这些发现可能会为未来的共情缺陷临床治疗研究提供信息。

Empathy, or the ability to detect and respond to the emotions of others, is a fundamental component of normal social communication and is necessary for the maintenance of social relationships. Many social cognitive disorders, including autism spectrum disorder, schizophrenia, and psychopathy, are characterized by empathy deficits, which impair normal social interaction and decrease quality of life. Nonetheless, the biological mechanisms that underlie empathy are poorly understood, and no medical interventions exist for the treatment of these deficits. Before such medical therapies can be developed, the significant gap in our knowledge about the biology of empathy must be addressed. A variety of recent studies have shown that many animals also have the capacity to detect and respond to the emotions of other animals. Therefore, this gap in knowledge can and should be addressed through the use of appropriate animal models that display empathy-based behaviors analogous to human behaviors. One common empathy-based response to the distress of others in humans is to provide consolation. Social response to distress in others is now known to be present in a small number of animal species, making it an ideal candidate behavior for learning more about the biology of empathy. Our laboratory has demonstrated for the first time that a laboratory rodent, the prairie vole, displays social response to distress under experimental conditions, that this behavior is empathy-based, and that the behavior is abolished through administration of an oxytocin (OT) receptor antagonist directly into the brain. Our lab is therefore uniquely positioned to discover the neurobiological basis of social response to distress in a way that is not possible in any other existing model. We propose to use social response to distress in the prairie vole as a model for learning about the neurobiology of empathy. In pursuit of this knowledge, we propose the following specific experiments. In Aim 1, we propose to locate one or more of the specific brain regions where OT receptor antagonist acts to prevent consolation. We will do so using site-specific infusions of the antagonist in combination with the social distress test developed in our pilot studies. In Aim 2, we will expand on this neural circuit by locating the source of OT release into the region of interest. We will do so using a triple-labeling technique to locate neurons that contain OT, project to the region of interest, and are active during social response to distress. In Aim 3, we propose to determine how natural variations in OT receptor density during development impact consolation. To determine this, we will experimentally manipulate the density of OT receptors in juvenile prairie voles using viral vector techniques developed in our laboratory, and measure the impact of these manipulations at adulthood on social response to distress. The results of these experiments will begin to bridge the gap in our knowledge of empathy by providing the first evidence of a behavioral circuit for social response to distress in the prairie vole. The proposed experiments will expand our knowledge of social cognition and the neurobiology of social response to distress. In addition, these findings may inform future studies into the clinical treatment of empathy deficits.