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: 10471205
• 负责人: Linda Amarante
• 金额: $ 0.16万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10471205
• 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.

项目摘要 为了灵活地执行行为，是根据以前的结果做出选择的，这些结果将最大化奖励。 至关重要的是，学习每个行动获得奖励的价值被认为可以推动这一决策过程。 在基于价值的决策框架中，这些值首先计算，然后用于选择和 执行操作。在许多神经精神疾病中，这种决策过程中的功能障碍很明显 包括成瘾和额叶皮质损伤的患者表现出无法灵活调整或适应的患者 他们的行为。从内侧前额叶皮层（MPFC）到其下游靶标的皮质纹状体途径 背侧纹状体（DMS）是涉及促进柔性行为的候选电路。神经相关 在跨物种的MPFC中发现了价值，传统上认为DMS参与了行动 选择，在DMS神经元中发现动作值的表示。但是，还不清楚 然后，如何将价值表示形式转换为自适应行为的实际运动。 同样，许多描述了任何一个区域中价值表示的研究已经完成了 离散的行为二进制测量和仅将神经活动与动作的终点相关联（例如发射 舔左或右喷嘴，或者将扫视到目标）。该项目将调查 通过调查MPFC和DMS神经活动如何代表正在进行的价值，对小鼠的作用进行价值 运动（AIM 1），并将揭示皮质纹状体途径内的特定细胞类型和途径 对于价值表示和行动选择是必需的（AIM 2）。在这两个目标中，MPFC的动作潜力 DMS将记录为渴的头部固定小鼠，以动态的觅食任务执行，需要操纵杆 搜索高概率奖励的运动，高概率奖励的位置变化 随着时间的推移。基于价值的决策变量，例如行动值和相对价值，将由 将动物的操纵杆运动行为与两个区域的神经活动相关联（AIM 1）。这将揭示 MPFC和DMS如何计算持续运动期间的决策变量。 AIM 2将揭示特定的 MPFC和DMS之间的神经电路； MPFC第5层的扰动将揭示 如何在皮质纹状体途径中以及使用转基因中表示基于价值的决策变量 小鼠系与抗体刺激配对，DMS中的直接和间接途径神经元将被鉴定为 确定每个单元格在表示价值和将价值转换为动作中的作用。这个项目总体将 对在决策过程中如何归因于行动的价值如何更好地理解 将确定皮质纹状体途径中的特定细胞如何计算和将有关值的信息转换为 做出最佳选择。