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

摘要 神经肽对社会认知至关重要，并被积极用作治疗高血压的药物。 治疗有明显社会缺陷的疾病，如自闭症谱系障碍(ASD)、精神分裂症和 精神变态。催产素(OT)是一种进化保守的神经肽，参与人类的社会加工过程。 多种物种。尽管有许多催产素诱导的社会行为的演示，但催产素是如何诱导的仍不清楚 调节参与社会决策的神经元网络。使用奖励捐赠任务涉及 在供体和受体猴身上，我们报告了吸入催产素可增强供体的替代强化 当在奖励他人和不奖励任何人之间做出选择时，而当 选择是在奖励自己和奖励他人之间做出的。这项任务中的Ot还增强了在 奖励捐款后的收件人。与同理心相关的加工可能受一组网络的调节 累及杏仁核、前扣带回(ACC)和眶前叶皮质(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赏，而OFC神经元 主要是指给予自己的奖励。杏仁核含有大量的催产素受体， 调节情感和社交过程。杏仁核，尤其是基底外侧核，是相互作用的。 与ACC和OFC有关，并参与评估积极和消极的奖励。不直接 在杏仁核与其他结构一起进行信息处理，并影响杏仁核的激活 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，我们试图通过以下方式澄清以下问题 利用奖赏捐赠任务：1)奖赏分配过程中单个杏仁核神经元的活动 决定；2)催产素在杏仁核神经元中诱导反应的神经机制；以及3)特定的调制 杏仁核对催产素介导的ACC和OFC神经元的影响。我们假设杏仁核 包含替代和自我强化信号，这两种信号都被吸入催产素放大。我们进一步 假设局部向杏仁核神经元传递OT增强了OFC和替换性神经元的自我奖赏信号 Acc中的奖励信号。我们的研究结果有可能促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。

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.