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.

项目摘要 大多数哺乳动物，包括人类，都有一种追求回报的动力， 食物、水和社会互动。社会刺激可以起到积极的促进作用，驱使动物去追求， 与自己物种的其他成员相互作用（例如，人们经常和朋友或老鼠出去玩， 重复访问以研究新的同种）。值得注意的是，缺乏社交动机， 奖励刺激和社会奖励处理的缺陷与几种疾病有关，如自闭症 光谱紊乱虽然非社会奖励相关行为的神经基质（例如，食品 奖励）已经被广泛研究，类似的研究对于社会奖励来说更困难，因为 社会互动的内在复杂性。目前还不清楚大脑处理信息的方式是否存在差异 社会奖励与非社会奖励。此外，虽然鼻内催产素释放会降低社会动机， 自闭症患者的缺陷，催产素如何调节神经回路介导的社会奖励相关 行为仍然知之甚少。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 光遗传学与一种新的操作性行为范式，以彻底和系统地映射如何社会和 非社会性奖励在内侧前额叶皮层（AIM 1a）中表现。我们将确定是否mPFC 奖励表征是由动物的内部状态调节的。(AIM 1 b）。我们将评估催产素 输入通过对前额叶皮层的活动进行成像来调节前额叶皮层中的社会和非社会奖励表征 神经元，同时沉默催产素输入mPFC（AIM 2）。最后，我们将确定社会奖励是否 表示，如接近社会奖励，效价，和奖励预测误差是功能性的 聚集在mPFC投影人群中（AIM 3）。总之，这项研究将帮助我们识别差异， 大脑如何编码社会奖励与非社会奖励的相似之处，以及动物的内部 国家调节这些表征。此外，考虑到使用 对患有自闭症的儿童和成人鼻内施用催产素，阐明催产素对 mPFC功能将是自闭症研究界的一个有价值的补充。