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.

项目概要 大多数哺乳动物，包括人类，其生活都是由寻求奖励的驱动力所驱动和塑造的，例如 食物、水和社交互动。社会刺激可以作为积极的强化物，驱使动物去追求和 与自己物种的其他成员互动（例如，人们经常与朋友或老鼠一起出去玩） 反复访问以调查小说同种）。值得注意的是，缺乏寻求社交的动力 奖励刺激和社会奖励处理缺陷与多种疾病有关，例如自闭症 频谱障碍。虽然非社会奖励相关行为（例如食物 奖励）已被广泛研究，但对于社会奖励的类似研究更加困难，因为 社会互动的固有复杂性。目前尚不清楚大脑的处理方式是否存在差异 社会奖励与非社会奖励。此外，尽管鼻内催产素递送会减轻社交动机 自闭症人类受试者的缺陷，催产素如何调节介导社会奖励相关的神经回路 行为仍然知之甚少。因此，解决这些问题将产生巨大的后果 为了人类的健康。 我们希望通过结合细胞分辨率成像技术和 光遗传学具有新颖的操作行为范式，可以彻底、系统地描绘社会和 非社交奖励由内侧前额叶皮层 (AIM 1a) 代表。我们将确定 mPFC 是否 奖励表征是由动物的内部状态调节的。 （目标 1b）。我们将评估催产素如何 输入通过对 mPFC 的活动进行成像来调节 mPFC 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 诸如社会奖励的接近度、效价和奖励预测误差之类的表示在功能上是 聚集在 mPFC 预测人群 (AIM 3) 中。总之，这项研究将帮助我们识别差异并 大脑如何编码社会奖励与非社会奖励以及动物的内部机制的相似之处 状态调节这些表示。此外，考虑到使用的有希望的治疗可能性 对患有自闭症的儿童和成人进行鼻内催产素给药，阐明催产素对自闭症的作用 mPFC 功能将成为自闭症研究界的一个有价值的补充。