Prefrontal circuits in processing social versus non-social rewards

处理社交与非社交奖励的前额回路

• 批准号: 10660240
• 负责人: Malavika Murugan
• 金额: $ 38.13万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-03 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660240
• 关键词: Address; Amygdaloid structure; Animals; Automobile Driving; Behavior; Behavioral; Behavioral Paradigm; Biological Assay; Brain; Color; Communities; Development; Diagnosis; Dimensions; Disease; Food; Friends; Glutamates; Health; Human; Image; Imaging Techniques; Individual; Interneurons; Knowledge; Life; Loneliness; Mammals; Maps; Medial; Mediating; Microscope; Motivation; Mus; Neurons; Nucleus Accumbens; Oxytocin; Patients; Persons; Play; Population; Population Projection; Positive Reinforcer; Prefrontal Cortex; Process; Research; Resolution; Rewards; Role; Route; Shapes; Social Behavior; Social Interaction; Stimulus; Sucrose; Testing; Therapeutic; Thirst; Ventral Tegmental Area; Visit; Water; adult with autism spectrum disorder; autism spectrum disorder; autistic children; human subject; imaging modality; member; neural; neural circuit; neural correlate; novel; optogenetics; response; reward circuitry; reward processing; social; social deficits

PROJECT SUMMARY Most mammals, including humans, navigate a life motivated and shaped by a drive to seek rewards such as food, water, and social interactions. Social stimuli can act as positive reinforcers, driving animals to pursue and interact with other members of their own species (e.g., people regularly hanging out with friends or a mouse repeatedly visiting to investigate a novel conspecific). Significantly, deficits in motivation to seek socially rewarding stimuli and deficits in social reward processing are associated with several disorders, such as Autism Spectrum Disorders. While the neural substrates underlying non-social reward-related behaviors (e.g., food rewards) have been studied extensively, similar studies have been more difficult for social rewards because of the inherent complexity of social interactions. It is unclear if there are differences in how the brain processes social versus non-social rewards. Additionally, although intranasal oxytocin delivery alleviates social motivation deficits in human subjects with autism, how oxytocin modulates neural circuits mediating social reward-related behaviors remains poorly understood. Therefore, addressing these questions will have immense consequences for human health. We hope to address these gaps in knowledge by combining cellular resolution imaging techniques and optogenetics with a novel operant behavioral paradigm to thoroughly and systematically map how social and non-social rewards are represented in the medial prefrontal cortex (AIM 1a). We will determine if the mPFC reward representations are modulated by the internal state of the animal. (AIM 1b). We will evaluate how oxytocin inputs modulate social and non-social reward representations in the mPFC by imaging the activity of mPFC neurons while silencing oxytocin inputs to the mPFC (AIM 2). Finally, we will determine if social reward representations such as proximity of social reward, valence, and reward prediction error are functionally clustered in mPFC projection populations (AIM 3). In summary, this research will help us identify differences and similarities in how the brain encodes social rewards versus non-social rewards and how the animal's internal state modulates these representations. Additionally, given the promising therapeutic possibility of using intranasal oxytocin administration to children and adults with autism, elucidation of the role of the oxytocin on mPFC function will be a valuable addition to the autism research community.

项目总结 大多数哺乳动物，包括人类，过着一种追求回报的驱动力和塑造的生活，比如 食物、水和社会互动。社会刺激可以作为积极的增强剂，驱使动物追逐和 与自己种族的其他成员互动(例如，人们经常与朋友或鼠标一起出去玩 反复访问以调查一部同种小说)。值得注意的是，缺乏寻求社交的动机 奖赏刺激和社会奖赏加工缺陷与几种障碍有关，如自闭症 谱系障碍。而非社会奖励相关行为(如食物)的神经基础 奖励)已经得到了广泛的研究，类似的研究更难获得社会奖励，因为 社会互动的内在复杂性。目前还不清楚大脑的处理方式是否存在差异 社会性回报与非社会性回报。此外，尽管鼻腔注射催产素减轻了社会动机 自闭症受试者的缺陷，催产素如何调节调节社会奖励相关的神经回路 人们对其行为仍知之甚少。因此，解决这些问题将产生巨大的后果。 为了人类健康。 我们希望通过结合细胞分辨率成像技术和 光遗传学使用一种新的操作行为范式来彻底和系统地描绘社会和 非社会奖励出现在内侧前额叶皮质(AIM 1a)。我们将确定mPFC是否 奖励表征受动物内部状态的影响。(目标1b)。我们将评估催产素如何 输入通过想象mPFC的活动来调节mPFC中的社会性和非社会性奖励表征 静息催产素传入mPFC的神经元(AIM 2)。最后，我们将确定社会奖励是否 诸如社会奖励的贴近度、价位和奖励预测误差等表示在功能上是 聚集在mPFC预测种群中(AIM 3)。总而言之，这项研究将帮助我们识别差异和 大脑编码社会奖赏和非社会奖赏的方式以及动物内部 国家对这些表述进行了调整。此外，鉴于使用的前景看好的治疗可能性 儿童和成人自闭症患者鼻腔注射催产素，阐明催产素在 MPFC功能将是自闭症研究社区的宝贵补充。