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: 10743875
• 负责人: Linda Amarante
• 金额: $ 7.1万
• 依托单位: ALLEN INSTITUTE
• 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/10743875
• 关键词: Converting; Value; into; Action; Computations

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.

项目总结 为了灵活地执行行为，会根据先前的结果做出选择，从而使回报最大化。 至关重要的是，了解每一项行动的价值以获得奖励被认为是推动这一决策过程的因素。 在基于价值的决策框架中，首先计算这些值，然后使用它们来选择和 执行操作。这一决策过程中的功能障碍在许多神经精神障碍中都很明显。 包括成瘾和额叶皮质损伤患者表现出无法灵活调整或适应 他们的行为。皮质纹状体通路，从内侧前额叶皮质(MPFC)到其下游目标， 背内侧纹状体(DMS)是促进灵活行为的候选回路。神经关联性 在不同物种的mPFC中都发现了有价值的物质，DMS传统上被认为参与了行动 选择，在DMS神经元中已经发现了动作值的表示。然而，目前还不清楚 确切地说，价值的表示然后如何转化为适应行为的实际运动。 类似地，许多描述这两个地区的价值表示的研究都是使用 行为的离散二进制测量，并仅将神经活动与动作的终点关联(例如，发出 舔左边或右边的喷嘴，或向目标扫视)。该项目将调查 通过研究mPFC和DMS神经活动如何在进行中代表价值，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中特定的细胞类型和通路， 是价值表示和行动选择所必需的(目标2)。在这两个目标中，来自mPFC的动作电位 DMS将被记录为口渴的头部固定小鼠在需要操纵杆的动态觅食任务中执行 移动搜索高概率奖励，其中高概率奖励的位置发生变化 随着时间的推移。基于值的决策变量，如操作值和相对值，将由 将动物的操纵杆运动行为与这两个区域的神经活动联系起来(目标1)。这将揭示 MPFC和DMS如何在持续移动过程中计算决策变量。目标2将揭示具体的 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 与逆行刺激配对的小鼠系，DMS中的直接和间接通路神经元将被识别为 确定每种细胞类型在代表价值和将价值转化为行动中的作用。这一项目总体上将 更好地理解在决策过程中如何将价值归因于行动，以及 将确定皮质纹状体通路中的特定细胞如何计算和转换关于价值的信息 做出最佳选择。