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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

基本信息

批准号：
10451614
负责人：
Elizabeth N. Holly
金额：
$ 6.59万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10451614
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 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

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.

项目总结/文摘