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: 8878644
• 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 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8878644
• 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，并且正在积极地作为治疗剂 用明显的社会缺陷治疗疾病，例如自闭症谱系障碍（ASD），精神分裂症和 精神病。催产素（OT）是参与社会加工的进化保守的神经肽 多种物种。尽管大量证明了OT引起的社会行为，但尚不清楚OT如何 调节参与社会决策的神经元网络。使用涉及的奖励捐赠任务 捐赠者和接收者猴子，我们报告说吸入的OT增强了供体的替代增强 当选择在奖励另一个人和没有人之间，而它会放大自我强化 选择是在奖励自己和另一个之间的奖励之间。此任务中的ot还可以增强外观行为 奖励捐赠后的收件人。与移情相关的处理可能是由一系列网络介导的 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的奖励，而OFC神经元 主要代表带给自我的奖励。杏仁核包含大量的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 与ACC和OFC相关，并参与评估正奖励和负奖励。直接 大门在杏仁核中使用其他结构处理，并影响杏仁核激活 人类的社会评估。至关重要的是，ASD的OT受体风险等位基因载体显示出改变的杏仁核 社交情感任务的激活。鉴于这些观察，我们试图通过 利用奖励捐赠任务：1）奖励分配过程中单个杏仁核神经元的活动 决定； 2）杏仁核神经元中OT诱导反应的神经机制； 3）特定的调制 杏仁核引起的ACC和OFC神经元的OFC神经元。我们假设杏仁核 既包含替代和自我增强信号，又被吸入的OT放大。我们进一步 假设本地OT向杏仁核神经元交付会增强OFC和替代性的自我奖励信号 ACC中的奖励信号。我们的结果有可能提高我们对神经精神疾病的了解 有社会缺陷以及我们对基于OT的治疗剂的理解。