Role of Oxytocin in the Amygdala-Prefrontal Network During Social Decision-Making

催产素在社会决策过程中杏仁核前额叶网络中的作用

• 批准号: 8894608
• 负责人: Steve Wohn Chul Chang
• 金额: $ 24.9万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8894608
• 关键词: Affective; Amygdaloid structure; Animal Model; Anterior; Area; Behavior; Behavioral; Brain; Breathing; Cues; Decision Making; Disease; Emotional; Empathy; Evaluation; Functional disorder; Human; Individual; Injection of therapeutic agent; Intervention; Juice; Knowledge; Mediating; Monkeys; Neurons; Neuropeptides; Outcome; Oxytocin; Oxytocin Receptor; Placebos; Population; Process; Psychological reinforcement; Reporting; Rewards; Role; Schizophrenia; Signal Transduction; Site; Social Behavior; Social Interaction; Specificity; Structure; Testing; Therapeutic; Therapeutic Agents; Variant; Vasopressins; abstracting; autism spectrum disorder; base; behavior test; cingulate cortex; cohort; information processing; microstimulation; neuromechanism; neuropsychiatry; preference; psychopathic personality; public health relevance; response; risk variant; social; social cognition; tool

Abstract Neuropeptides are critical for social cognition, and are actively being pursued as a therapeutic agent for treating diseases with marked social deficits, such as autism spectrum disorders (ASD), schizophrenia, and psychopathy. Oxytocin (OT) is an evolutionarily conserved neuropeptide involved in social processing in multiple species. Despite numerous demonstrations of OT-induced social behavior, it remains unclear how OT modulates networks of neurons involved in social decision-making. Using the reward donation task involving donor and recipient monkeys, we reported that inhaled OT enhances vicarious reinforcement of the donor when the choice is between rewarding another and no one, whereas it amplifies self reinforcement when the choice is between rewarding himself and another. OT in this task also enhances the looking behavior at the recipient following reward donations. Empathy-related processing might be mediated by a cohort of networks involving amygdala, anterior cingulate (ACC), and orbitofrontal cortices (OFC). In the reward donation task, we also found that ACC neurons predominantly represent rewards delivered to another, whereas OFC neurons predominantly represent rewards delivered to self. Amygdala contains a high number of OT receptors, and mediates affective and social processing. Amygdala, especially the basolateral portion, is reciprocally connected with ACC and OFC, and is involved in evaluating both positive and negative rewards. OT directly gates information processing in amygdala with other structures, and influences amygdala activations during social evaluations in humans. Critically, OT receptor risk allele carriers for ASD show altered amygdala activations in social emotional tasks. Given these observations, we seek to elucidate the following by capitalizing upon the reward donation task: 1) activity of single amygdala neurons during reward allocation decisions; 2) neural mechanisms of OT-induced responses in amygdala neurons; and 3) specific modulations of ACC and OFC neurons due to OT-mediated processes by amygdala. We hypothesize that amygdala contains both vicarious and self reinforcement signals, and these are both amplified by inhaled OT. We further hypothesize that local OT delivery to amygdala neurons enhances self reward signals in OFC and vicarious reward signals in ACC. Our results have a potential to advance our knowledge on neuropsychiatric diseases with social deficits, and our understanding of OT-based therapeutics.

抽象的 神经肽对于社会认知至关重要，并且正在积极寻求作为以下疾病的治疗剂： 治疗具有明显社交缺陷的疾病，例如自闭症谱系障碍 (ASD)、精神分裂症和 精神病。催产素（OT）是一种进化上保守的神经肽，参与社会处理 多个物种。尽管有大量关于 OT 引发的社会行为的示范，但仍不清楚 OT 是如何产生的 调节参与社会决策的神经元网络。使用奖励捐赠任务涉及 供体猴和受体猴，我们报告吸入 OT 增强了供体猴的替代强化 当在奖励他人和不奖励他人之间做出选择时，当 选择是在奖励自己和奖励他人之间。此任务中的 OT 还增强了观察对象的观看行为 奖励捐赠后的接受者。与同理心相关的处理可能是由一组网络介导的 涉及杏仁核、前扣带回 (ACC) 和眶额皮质 (OFC)。在奖励捐赠任务中，我们 还发现 ACC 神经元主要代表传递给另一个神经元的奖励，而 OFC 神经元 主要代表给予自我的奖励。杏仁核含有大量 OT 受体，并且 调解情感和社会处理。杏仁核，尤其是基底外侧部分，是相互 与 ACC 和 OFC 连接，并参与评估正面和负面奖励。直接OT 控制杏仁核与其他结构的信息处理，并影响杏仁核的激活 对人类的社会评价。至关重要的是，自闭症谱系障碍 (ASD) OT 受体风险等位基因携带者显示杏仁核发生改变 社会情感任务的激活。鉴于这些观察结果，我们试图通过以下方式阐明以下内容： 利用奖励捐赠任务：1）奖励分配期间单个杏仁核神经元的活动 决定； 2）OT诱导杏仁核神经元反应的神经机制； 3）特定调制 ACC 和 OFC 神经元由于杏仁核 OT 介导的过程而受到影响。我们假设杏仁核 包含替代信号和自我强化信号，并且这些信号都会被吸入的 OT 放大。我们进一步 假设局部 OT 传递至杏仁核神经元可增强 OFC 和替代神经元中的自我奖赏信号 ACC 中的奖励信号。我们的结果有可能增进我们对神经精神疾病的了解 社会缺陷以及我们对基于 OT 的疗法的理解。