Converting Value into Action: Computations in Corticostriatal Circuits for Flexible Decision Making

将价值转化为行动：用于灵活决策的皮质纹状体回路计算

• 批准号: 10314166
• 负责人: Linda Amarante
• 金额: $ 7.1万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-11 至 2024-08-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10314166
• 关键词: Action Potentials; Adaptive Behaviors; Animals; Area; Basal Ganglia; Behavior; Brain; Cells; Corpus striatum structure; Decision Making; Exhibits; Functional disorder; Harvest; Head; Joystick; Label; Learning; Left; Location; Maps; Measures; Medial; Motor output; Movement; Mus; Neocortex; Neurons; Outcome; Output; Pathway interactions; Patients; Prefrontal Cortex; Probability; Process; Pyramidal Tracts; Rewards; Role; Saccades; Synapses; Testing; Time; Transgenic Mice; Update; Work; addiction; base; cell type; cognitive function; experience; experimental study; flexibility; insight; neural circuit; neural correlate; neurochemistry; neuropsychiatric disorder; optogenetics; prevent; relating to nervous system; striosome; theories

PROJECT SUMMARY To flexibly execute behavior, choices are made based on previous outcomes that will maximize reward. Crucially, learning the value of each action to obtain a reward is thought to drive this decision making process. In a value-based decision making framework, these values are first computed and then used to select and execute actions. Dysfunction in this decision making process is evident in many neuropsychiatric disorders including addiction and in patients with frontal cortical damage who show an inability to flexibly adjust or adapt their behavior. The corticostriatal pathway, from the medial prefrontal cortex (mPFC) to its downstream target, dorsomedial striatum (DMS), is a candidate circuit implicated in promoting flexible behavior. Neural correlates of value have been found in mPFC across species, and DMS is traditionally thought to be involved in action selection, where representations of action values have been found in DMS neurons. However, it is unclear exactly how representations of value are then transformed into actual movements for adaptive behavior. Similarly, many studies that have described representations of value in either region have done so using discrete binary measures of behavior and correlate neural activity only to the action's endpoint (e.g. emitting a lick at a left or right spout, or making a saccade to a target). This project will investigate the transformation of value into actions in mice by investigating how mPFC and DMS neural activity represent value during ongoing movements (Aim 1), and will reveal the specific cell types and pathways within the corticostriatal pathway that are necessary for value representation and action selection (Aim 2). In both aims, action potentials from mPFC and DMS will be recorded as thirsty head-fixed mice perform in a dynamic foraging task that requires a joystick movement to search for the high-probability reward, where the location of the high-probability reward changes over time. Value-based decision variables, such as action values and relative value, will be quantified by correlating the animal's joystick movement behavior to neural activity in both areas (Aim 1). This will reveal how mPFC and DMS compute decision variables during ongoing movements. Aim 2 will reveal the specific neural circuitry between mPFC and DMS; perturbations of mPFC layer 5 pyramidal tract neurons will reveal how value-based decision variables are represented in the corticostriatal pathway, and by using transgenic mouse lines paired with antidromic stimulation, direct and indirect pathway neurons in DMS will be identified to determine each cell type's role in representing value and transforming value into action. This project overall will provide a better understanding of how values are attributed to actions during the decision making process, and will identify how specific cells in the corticostriatal pathway compute and transform information about value to make optimal choices.

项目概要 为了灵活地执行行为，根据先前的结果做出选择，以最大化奖励。 至关重要的是，了解每个行动的价值以获得奖励被认为可以推动这一决策过程。 在基于价值的决策框架中，首先计算这些值，然后用于选择和 执行行动。在许多神经精神疾病中，这一决策过程的功能障碍很明显 包括成瘾以及额叶皮质损伤且无法灵活调整或适应的患者 他们的行为。皮质纹状体通路，从内侧前额叶皮层 (mPFC) 到其下游目标， 背内侧纹状体（DMS）是与促进灵活行为有关的候选回路。神经关联 在跨物种的 mPFC 中发现了重要价值，传统上认为 DMS 参与了行动 选择，在 DMS 神经元中发现了动作值的表示。然而尚不清楚 价值的表征如何转化为适应性行为的实际运动。 同样，许多描述任一地区价值表征的研究都是使用 行为的离散二元测量，并将神经活动仅与动作的终点相关联（例如发出 舔左或右喷口，或向目标扫视）。该项目将研究改造 通过研究 mPFC 和 DMS 神经活动如何在持续过程中代表价值，将价值转化为小鼠的行动 运动（目标 1），并将揭示皮质纹状体通路内的特定细胞类型和通路， 对于价值表达和行动选择（目标 2）是必要的。在这两个目标中，mPFC 的行动潜力 当口渴的头部固定小鼠执行需要操纵杆的动态觅食任务时，DMS 将被记录 寻找高概率奖励的运动，其中高概率奖励的位置发生变化 随着时间的推移。基于价值的决策变量，例如行动价值和相对价值，将通过以下方式量化 将动物的操纵杆运动行为与这两个区域的神经活动相关联（目标 1）。这将揭示 mPFC 和 DMS 如何在持续运动期间计算决策变量。目标2将揭示具体 mPFC 和 DMS 之间的神经回路； mPFC 第 5 层锥体束神经元的扰动将揭示 基于价值的决策变量如何在皮质纹状体通路中表示，以及通过使用转基因 与逆向刺激配对的小鼠品系，DMS 中的直接和间接通路神经元将被鉴定为 确定每种细胞类型在代表价值并将价值转化为行动方面的作用。本项目总体将 更好地理解决策过程中如何将价值归因于行动，以及 将识别皮质纹状体通路中的特定细胞如何计算和转换有关价值的信息 做出最优选择。