The Role of the Locus Coeruleus-Norepinephrine System in Flexible Decision-Making

蓝斑-去甲肾上腺素系统在灵活决策中的作用

• 批准号: 10818825
• 负责人: Benjamin B Scott
• 金额: $ 41.25万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-13 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818825
• 关键词: Address; Affect; Behavior; Behavioral; Calcium; Cerebral cortex; Cognition; Cognition Disorders; Cognitive; Color; Complex; Computer Models; Data; Decision Making; Dependovirus; Development; Diagnosis; Disease; Enhancers; Environment; Foundations; Genetic Markers; Human; Image; Imaging Device; Immediate-Early Genes; Immunohistochemistry; Impulsivity; Individual; Injections; Knowledge; Link; Measurement; Measures; Mental disorders; Modeling; Mood Disorders; Motor Cortex; Nervous System; Neurodevelopmental Disorder; Neurons; Norepinephrine; Organism; Output; Pattern; Physiological; Physiology; Play; Population Dynamics; Process; Public Health; Rattus; Research; Resolution; Rodent; Role; Sensory; Signal Transduction; System; Testing; Training; Visual Cortex; Work; cell type; designer receptors exclusively activated by designer drugs; experimental study; flexibility; genetic effector; genetic manipulation; improved; in vivo; in vivo imaging; in vivo optical imaging; information processing; locus ceruleus structure; neural; neural circuit; neural model; neuroimaging; neuromechanism; neuropsychiatric disorder; norepinephrine system; novel; pharmacologic; predictive modeling; redshift; response; role model; selective expression; sensor; sensory cortex; sensory input; spectrograph; theories; tool

PROJECT SUMMARY/ABSTRACT Flexible decision making, in which individuals adapt their decision strategies, is a hallmark of human cognition. In particular, humans are able to shift between impulsive (fast, but inaccurate) and deliberative (accurate, but slow) strategies based on situational demands. Observations that this capacity is disrupted in neuropsychiatric disorders motivates the study of the neural mechanisms that regulate this type of flexible decision making. Previous studies suggest that locus-coeruleus norepinephrine (LC-NE) system may play a key role in flexibly switching between impulsive and deliberative decision making. However, we still lack a precise, circuit-level understanding of how the NE-LC system alters information processing in downstream targets to effect decision making. To address this gap in knowledge, we propose to utilize a rat model of flexible decision making to identify how NE-LC alters information processing during flexible decision making. Specifically, we aim to test predictions of a leading computational model, the adaptive gain theory model, which posits that high NE tone alters the gain of information processing in neurons of the cerebral cortex leading to impulsive decision making. Our proposal is separated into three aims. In the first aim, we will use cellular resolution imaging of LC-NE activity and NE release to determine whether changes in NE signaling correlate with changes in impulsivity as organisms respond to environmental demands. In the second aim, we will manipulate the activity of NE neurons in the LC using chemogenics and evaluate whether artificial activation and silencing of LC-NE system is sufficient to drive changes in impulsivity. In the third aim, we will use simultaneous imaging of neuronal dynamics and NE release to determine whether NE tone predicts the strength of cortical responses to decision-related sensory inputs. If successful, this project will achieve a circuit-level understanding of how NE signaling regulates flexible discission making. This improved understanding will provide a critical advance in identifying the neural mechanism of decision making and will provide a foundation for understanding how these mechanisms may be affected in neuropsychiatric disorders.

项目总结/摘要 灵活决策是指个体根据自身的决策策略进行调整，是人类社会的一个标志。 认知.特别是，人类能够在冲动（快速，但不准确）和审慎之间转换 （准确，但缓慢）基于情境需求的战略。观察到这种能力在 神经精神障碍促使人们研究调节这种灵活的神经机制。 决策。以往的研究表明，蓝斑-去甲肾上腺素（LC-NE）系统可能在脑缺血再灌注损伤中起关键作用 在冲动决策和审慎决策之间灵活切换的角色。然而，我们仍然缺乏一个精确的， 电路级理解NE-LC系统如何改变下游目标的信息处理， 影响决策。 为了解决这一知识差距，我们建议利用灵活决策的大鼠模型来识别 NE-LC如何在灵活决策过程中改变信息处理。具体来说，我们的目标是测试预测 一个领先的计算模型，自适应增益理论模型，假设高NE音改变增益 大脑皮层神经元的信息处理导致冲动决策。我们的建议 分为三个目标。在第一个目标中，我们将使用LC-NE活性和NE的细胞分辨率成像。 释放，以确定NE信号传导的变化是否与生物体冲动性的变化相关 响应环境需求。在第二个目标中，我们将操纵LC中NE神经元的活动 使用化学发生学，并评估LC-NE系统的人工激活和沉默是否足以驱动 冲动的变化。在第三个目标中，我们将使用神经元动力学和NE释放的同步成像 以确定NE音调是否预测皮质对决策相关感觉输入的反应强度。如果 如果成功，该项目将实现对NE信令如何调节灵活断开的电路级理解 制作。这种更好的理解将为识别神经机制提供关键性的进展。 决策，并将为理解这些机制如何受到影响提供基础， 神经精神障碍