Effects 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

基本信息

批准号：
10643893
负责人：
Elizabeth N. Holly
金额：
$ 17.99万
依托单位：
RUTGERS THE STATE UNIV OF NJ NEWARK
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10643893
关键词：
Adolescence Adolescent Adult Affect Automobile Driving Award Behavior Behavioral COVID-19 COVID-19 impact 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 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 Signal Transduction Social Development Social Interaction Social isolation Stimulus Stress Synapses Techniques Testing Thalamic structure Training Work career cognitive development cost discounting expectation experimental study flexibility in vivo male neural neural circuit neural network optogenetics physical conditioning response school closure stay-at-home order tenure track

项目摘要

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.

项目概要/摘要青春期是社会和认知发展的一个特别重要的时期，其特点是部分原因是探索、社交互动和神经连接的快速增长。社会的青春期的孤立对一系列行为和行为有着明显而深远的影响。生理终点延伸至成年期。本次研究的总体目标是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的行为成年期的决策，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。这项工作非常及时且至关重要，因为 COVID-19 已越来越多的青少年因学校关闭而陷入社会孤立居家令。该提案的第一个目标是利用操作性任务来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整合预期成本决策。初步数据表明，青少年的社会孤立放大了奖励价值，但决策行为的具体方面将与计算模型脱节基于价值的选择。第二个目标建立在这项行为工作的基础上，以检验以下假设：青少年社会隔离会扰乱成年期间的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背内侧纹状体（DMS）是该网络中的关键节点。前额叶输入来自内侧前额皮质 (mPFC) 和眶额皮质 (OFC) 的 DMS 至关重要分别在行动选择和结果评估中。这三个节点全部青春期经历成熟和完善，青春期社会孤立扰乱了这种发展。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) 和单单元记录将用于测试青少年社会隔离如何影响突触强度和连接在基于价值的决策行为期间，从这些皮质区域到 DMS。指导研究科学家发展奖中提出的这项工作将为伊丽莎白博士提供 Holly 接受过决策行为和体内计算建模方面的培训电生理学，这将成为她独立研究基础的重要组成部分职业。完成该奖项后，霍利博士的目标是过渡到终身教授职位教职职位并申请 R01。霍莉博士组建的导师团队将确保她这些技术的成功培训，并帮助她做好过渡到自己独立的准备研究实验室。