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

项目总结/摘要 青春期是社会和认知发展的一个特别重要的时期， 部分原因是探索、社会互动和神经连接的快速增长。社会 青少年时期的孤立对一系列行为和心理方面有着明确而深刻的影响， 生理终点延伸到成年期。这项研究的首要目标是 一项提案旨在阐明雄性和雌性小鼠的青少年社会隔离如何改变基于价值观的 成年期的决策，以及驱动这些决策的潜在皮质纹状体回路， 复杂的目标导向行为这项工作是及时和至关重要的，因为COVID-19已经 由于学校关闭，越来越多的青少年被社会孤立， 呆在家里的命令 本研究的第一个目的是利用操作性任务系统地研究青少年如何 社会隔离会影响小鼠后来如何评价奖励收益，并在 决策。初步数据表明，青少年的社会隔离放大了奖励价值， 但决策行为的特定方面将与计算建模相分离 基于价值的选择。第二个目标建立在这个行为工作的基础上，以检验假设， 青少年社会隔离在成年期扰乱皮质纹状体回路和纹状体输出 基于价值的决策。分布式神经网络在决策过程中参与， 而背内侧纹状体（DMS）是这个网络中的关键节点。前额叶输入 内侧前额叶皮层（mPFC）和眶额皮层（OFC）的DMS与脑内的运动密切相关， 在行动选择和结果评价，分别。这三个节点 在青少年时期经历成熟和完善，以及青少年社会隔离 破坏了这种发展。然而，这如何影响成人皮质纹状体功能仍然存在 未知使用体内电生理学、局部场电位（LFP）和单个单位记录 将被用来测试青少年的社会孤立如何影响突触的强度和连接性 在基于价值的决策行为中从这些皮层区域到DMS。 这项工作提出的指导研究科学家发展奖将提供博士伊丽莎白 冬青与培训的计算建模的决策行为和在体内 电生理学，这将是她独立研究基础的重要组成部分 事业通过完成这个奖项，我们的目标是博士冬青过渡到终身教职的轨道 教师职位，并申请R01。冬青博士组建的导师团队将确保她 成功的培训，这些技术，并准备她过渡到她自己的独立 研究实验室。

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.