The Neurobiology of Social Response to Distress

对痛苦的社会反应的神经生物学

• 批准号: 8769951
• 负责人: James Burkett
• 金额: $ 4.31万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8769951
• 关键词: Address; Adolescent; Adult; Animal Model; Animals; Anterior; Behavior; Behavior Therapy; Behavioral; Biological; Biology; Brain; Brain region; Caring; Cells; Characteristics; Clinical Treatment; Cognition Disorders; Data; Development; Disease; Distress; Emotions; Empathy; Fiber; Future; Goals; Hormones; Human; Hypothalamic structure; Individual; Infusion procedures; Injection of therapeutic agent; Intervention; Knowledge; Label; Laboratories; Lead; Learning; Literature; Maintenance; Measures; Mediating; Medical; Modeling; Mus; Neurobiology; Neurons; Nucleus Accumbens; Oxytocin; Oxytocin Receptor; Pan Genus; Pilot Projects; Play; Population; Positioning Attribute; Prefrontal Cortex; Quality of life; Relative (related person); Research; Research Proposals; Research Support; Rodent; Role; Schizophrenia; Site; Social Functioning; Social Interaction; Source; Staining method; Stains; Techniques; Testing; Time; Variant; Viral Vector; Work; autism spectrum disorder; base; behavioral study; density; driving behavior; effective intervention; insight; interest; learned behavior; loved ones; neural circuit; neurochemistry; novel; prairie vole; presynaptic; prevent; psychopathic personality; receptor; receptor density; receptor expression; relating to nervous system; research study; response; small hairpin RNA; social; social attachment; social cognition; social communication

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.

同理心，或者说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，都以同理心缺陷为特征，这会损害正常的社交互动并降低生活质量。尽管如此，人们对同理心背后的生物学机制知之甚少，并且不存在治疗这些缺陷的医疗干预措施。在开发此类医学疗法之前，必须解决我们在同理心生物学知识方面的巨大差距。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，这些动物模型表现出类似于人类行为的基于同理心的行为。人类对他人痛苦的一种常见的基于同理心的反应是提供安慰。现在已知少数动物物种存在对他人痛苦的社会反应，这使其成为更多了解同理心生物学的理想候选行为。我们的实验室首次证明，实验室啮齿动物草原田鼠在实验条件下表现出对痛苦的社会反应，这种行为是基于同理心的，并且通过直接向大脑施用催产素（OT）受体拮抗剂可以消除这种行为。因此，我们的实验室具有独特的优势，能够以任何其他现有模型不可能的方式发现对痛苦的社会反应的神经生物学基础。我们建议利用草原田鼠对痛苦的社会反应作为学习同理心神经生物学的模型。为了寻求这些知识，我们提出了以下具体实验。在目标 1 中，我们建议定位 OT 受体拮抗剂发挥作用以防止安慰的一个或多个特定大脑区域。我们将使用拮抗剂的特定位点输注结合我们在试点研究中开发的社会困扰测试来做到这一点。在目标 2 中，我们将通过将 OT 释放源定位到感兴趣的区域来扩展该神经回路。我们将使用三重标记技术来定位包含 OT、投射到感兴趣区域并在对痛苦的社会反应期间活跃的神经元。在目标 3 中，我们建议确定发育过程中 OT 受体密度的自然变化如何影响安慰。为了确定这一点，我们将使用我们实验室开发的病毒载体技术实验性地操纵幼年草原田鼠的 OT 受体密度，并测量这些操纵对成年期社会应激反应的影响。这些实验的结果将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，从而开始弥合我们在同理心知识方面的差距。拟议的实验将扩展我们对社会认知和对痛苦的社会反应的神经生物学的了解。此外，这些发现可能为未来同理心缺陷的临床治疗研究提供信息。