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.

摘要 神经肽对于社会认知是至关重要的，并且正被积极地追求作为治疗剂， 治疗具有显著社会缺陷的疾病，如自闭症谱系障碍（ASD）、精神分裂症， 精神变态催产素（OT）是一种进化上保守的神经肽，参与社会加工， 多个物种尽管有许多关于OT引起的社会行为的证明，但仍不清楚OT是如何引起的。 调节参与社会决策的神经元网络。使用奖励捐赠任务， 供体和受体猴，我们报告说，吸入OT增强替代强化供体 当选择是在奖励另一个人和没有人之间，而它放大了自我强化时， 在奖励自己和他人之间做出选择。OT在这项任务中也增强了在 接受捐赠后的奖励。共情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神经元主要代表奖励传递给另一个，而OFC神经元 主要代表了对自己的奖励。杏仁核含有大量的OT受体， 调节情感和社会处理。杏仁核，尤其是基底外侧部分， 与ACC和OFC相关，并参与评估积极和消极的奖励。OT直接 门控杏仁核与其他结构的信息处理，并影响杏仁核的激活过程中， 人类的社会评价。关键是，ASD的OT受体风险等位基因携带者显示杏仁核改变 在社交情绪任务中的激活。鉴于这些观察结果，我们试图通过以下方式澄清以下问题： 利用奖励捐赠任务：1）单个杏仁核神经元在奖励分配期间的活动 决定; 2）OT诱导杏仁核神经元反应的神经机制; 3）特异性调制 ACC和OFC神经元由于OT介导的杏仁核过程。我们假设杏仁核 包含替代和自我强化信号，这些信号都被吸入的OT放大。我们进一步 假设杏仁核神经元的局部OT传递增强了OFC和替代的自我奖赏信号， 我们的研究结果有可能促进我们对神经精神疾病的认识 以及我们对OT疗法的理解。