Effect of adolescent social isolation on adult decision making and corticostriatal circuitry

青少年社会隔离对成人决策和皮质纹状体回路的影响

• 批准号: 10282683
• 负责人: Elizabeth N. Holly
• 金额: $ 17.99万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10282683
• 关键词: Adolescence; Adolescent; Adult; Affect; Automobile Driving; Award; Behavior; Behavioral; COVID-19; Choice Behavior; Cognitive; Communication; Complex; Computer Models; Corpus striatum structure; Costs and Benefits; Coupling; Data; Decision Making; Dendritic Spines; Development; Electrophysiology (science); Ensure; Faculty; Female; Foundations; Goals; Habits; Holly; Home; Human; Impairment; Intervention; Laboratory Research; Learning; Life; Long-Term Effects; Measures; Medial; Mediating; Mental Health; Mentored Research Scientist Development Award; Mentorship; Modeling; Motivation; Motor; Mus; Neurons; Outcome; Output; Performance; Phase; Physiological; Positioning Attribute; Prefrontal Cortex; Process; Research; Rewards; Rodent; Schools; Signal Transduction; Social Development; Social Interaction; Social isolation; Stimulus; Stress; Synapses; Techniques; Testing; Thalamic structure; Time; Training; Work; base; career; cognitive development; cost; discounting; expectation; experimental study; flexibility; in vivo; male; neural circuit; neural network; optogenetics; physical conditioning; relating to nervous system; response; social; tenure track

PROJECT SUMMARY/ABSTRACT Adolescence is a particularly important period in social and cognitive development, characterized in part by rapid increases in exploration, social interaction, and neural connectivity. Social isolation in adolescence has a clear, profound impact on a wide range of behavioral and physiological endpoints extending into adulthood. The overarching research goal of this proposal is to elucidate how adolescent social isolation in male and female mice alters value-based decision making in adulthood, as well as the underlying corticostriatal circuitry driving these complex goal-directed behaviors. This work is timely and vitally important as COVID-19 has subjected an increasing number of adolescents to social isolation through school closures and stay-at-home orders. A first aim of this proposal is to use operant tasks to systematically investigate how adolescent social isolation impacts how mice later value reward benefits and integrate expected costs during decision making. Preliminary data suggests that adolescent social isolation amplifies reward value, but specific aspects of decision-making behavior will be disentangled with computational modeling of value-based choice. The second aim builds on this behavioral work to test the hypothesis that adolescent social isolation disrupts corticostriatal circuitry and striatal output during adult value-based decision-making. A distributed neural network is engaged during decision- making, and the dorsomedial striatum (DMS) is a key node in this network. Prefrontal inputs to the DMS from the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) are critically involved in action selection and outcome valuation, respectively. All three of these nodes undergo maturation and refinement during adolescence, and adolescent social isolation disrupts this development. However, how this impacts adult corticostriatal function remains unknown. Using in vivo electrophysiology, local field potential (LFP) and single- unit recordings will be used to test how adolescent social isolation affects synaptic strength and connectivity from these cortical regions to the DMS during value-based decision-making behavior. This work proposed in the Mentored Research Scientist Development Award will provide Dr. Elizabeth Holly with training in computational modeling of decision-making behavior and in vivo electrophysiology, which will be an important part of the foundation of her independent research career. By completion of this Award, the goal is for Dr. Holly to transition to a tenure-track faculty position and apply for an R01. The mentorship team Dr. Holly has assembled will ensure her successful training in these techniques, and prepare her to transition to her own independent research laboratory.

项目摘要/摘要 青春期是社会和认知发展中特别重要的时期 在某种程度上，探索，社会互动和神经连通性的快速增加。社会的 青春期的隔离对广泛的行为和 生理终点一直延伸至成年。总体研究目标 建议是阐明男性和雌性小鼠青少年社会隔离如何改变基于价值的 成年后的决策以及驱动这些的基础皮质纹状体电路 复杂的目标指导行为。这项工作及时且至关重要，因为Covid-19拥有 通过学校关闭，越来越多的青少年社会隔离， 在家订单。 该建议的第一个目的是使用操作任务系统地研究青少年 社会隔离会影响小鼠后来的价值奖励收益并整合预期成本 决策。初步数据表明，青少年的社会隔离会放大奖励价值， 但是，决策行为的具体方面将通过计算建模来解散 基于价值的选择。第二个目标是基于这项行为工作，以检验以下假设。 青少年社会隔离会破坏成人期间皮质纹状体电路和纹状体产量 基于价值的决策。在决策过程中参与分布式神经网络 - 制作和背侧纹状体（DMS）是该网络中的关键节点。前额叶输入 内侧前额叶皮层（MPFC）和Orbitrontal皮层（OFC）的DM非常涉及 在行动选择和结果估值中。这三个节点 在青春期和青少年社会隔离期间经历成熟和完善 破坏了这一发展。但是，这如何影响成人皮质纹状体功能 未知。使用体内电生理学，局部场电位（LFP）和单位记录 将用于测试青少年社会隔离如何影响突触强度和连通性 从这些皮质区域到基于价值的决策行为期间的DMS。 指导研究科学家发展奖提出的这项工作将为伊丽莎白博士提供。 冬青在决策行为和体内的计算建模培训中进行培训 电生理学，这将是她独立研究基础的重要组成部分 职业。通过完成该奖项，其目标是让Holly博士过渡到终身 教师职位并申请R01。霍莉博士组装的指导团队将确保她 在这些技术中成功培训，并准备她过渡到自己的独立 研究实验室。