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

描述（由申请人提供）：神经肽对于社会认知是关键的，并且正被积极地用作治疗具有显著社会缺陷的疾病的治疗剂，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，在许多物种中参与社会加工。尽管OT诱导的社会行为有许多证据，但OT如何调节参与社会决策的神经元网络仍不清楚。使用涉及捐赠者和接受者猴子的奖励捐赠任务，我们报告说，吸入OT增强了捐赠者的替代强化，当选择奖励另一个人和没有人之间时，而当选择奖励自己和另一个人时，它放大了自我强化。在这个任务中，OT也增强了在奖励捐赠后对接受者的注视行为。移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（ACC），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人的奖励，而OFC神经元主要代表传递给自己的奖励。杏仁核含有大量的OT受体，并介导情感和社会处理。杏仁核，尤其是基底外侧部分，与前扣带回和眶额皮层有着密切的联系，参与评价正性和负性奖赏。OT直接门控杏仁核与其他结构的信息处理，并影响杏仁核在人类社会评价过程中的激活。重要的是，自闭症的OT受体风险等位基因携带者在社会情绪任务中显示出杏仁核激活的改变。鉴于这些观察结果，我们试图通过利用奖励捐赠任务来阐明以下内容：1）单个杏仁核神经元在奖励分配决策过程中的活动; 2）杏仁核神经元中OT诱导反应的神经机制; 3）由于杏仁核OT介导的过程，ACC和OFC神经元的特异性调节。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，本地OT交付杏仁核神经元增强自我奖励信号OFC和替代奖励信号ACC. Our结果有可能推进我们的知识与社会缺陷的神经精神疾病，我们的理解OT为基础的治疗。 公共卫生相关性：尽管在行为上存在广泛的表型变异，但自闭症谱系障碍（ASD）患者在社会交往中存在核心缺陷。在这里，我们提出，ASD的社会功能障碍的结果，在一定程度上，从别人获得替代奖励的问题，这一过程可能取决于神经肽催产素，这是牵连在各种社会过程。我们将使用替代性奖励的动物模型来发现催产素（ASD的潜在治疗方法）如何介导大脑中的社会处理，并发现其在大脑功能障碍中的作用。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Despite a broad continuum of phenotypic variation in behavior, individuals with autism spectrum disorders (ASD) share core deficits in social interaction. Here we propose that social dysfunction in ASD results, in part, from problems in deriving vicarious reward from others, and that this process may depend on neuropeptide oxytocin, which is implicated in various social processes. We will use our animal model of vicarious reward to discover how oxytocin, a potential therapy for ASD, mediates social processing in the brain, and discover its role in brain dysfunction.