Behavioral Paradigms to Probe Individual Mouse Differences in Value-Based Decision Making
Behavioral Paradigms to Probe Individual Mouse Differences in Value-Based Decision Making
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DOI：
10.3389/fnins.2019.00050
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发表时间：
2019-02-07
影响因子：
4.3
通讯作者：
Fuccillo, Marc, V
中科院分区：
文献类型：
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作者：
Alabi, Opeyemi O.;Fortunato, Michael P.;Fuccillo, Marc, V
基于价值的决策依赖于分布式神经系统，该系统权衡行动的好处和获得给定结果所需的成本。这些系统的扰动被认为是许多神经精神障碍中动作选择异常的基础。小鼠的遗传工具为探索这些系统的细胞成分及其分子基础提供了一个很有希望的机会。然而，很少有任务被设计成强有力地描述单个老鼠在选择行动时如何将不同的奖励收益和成本结合在一起。在这里，我们提出了一个强迫选择，两种选择任务，其中每个选项都与一个特定的奖励结果和唯一的可操作偶发事件相关联。我们采用全球和个人试验方法来评估小鼠对不同的“选择利益”(模拟为不同的奖励幅度比率)和不同形式的“选择成本”(模拟为增加重复运动输出以获得奖励或增加延迟以获得奖励)的选择模式和行为灵活性。我们证明：(1)老鼠选择对结果的相对收益高度敏感；(2)在相对报酬差异较大的环境中，选择成本被大幅贴现；(3)不同的成本形态被差异地整合到行动选择中；(4)个体老鼠对奖励收益的敏感度与对奖励成本的敏感度相关。这些范式揭示了个体动物在基于价值的行为选择上的稳定差异，从而为询问目标导向功能障碍的神经回路和分子病理生理学提供了基础。
Value-based decision making relies on distributed neural systems that weigh the benefits of actions against the cost required to obtain a given outcome. Perturbations of these systems are thought to underlie abnormalities in action selection seen across many neuropsychiatric disorders. Genetic tools in mice provide a promising opportunity to explore the cellular components of these systems and their molecular foundations. However, few tasks have been designed that robustly characterize how individual mice integrate differential reward benefits and cost in their selection of actions. Here we present a forced-choice, two-alternative task in which each option is associated with a specific reward outcome, and unique operant contingency. We employed global and individual trial measures to assess the choice patterns and behavioral flexibility of mice in response to differing "choice benefits" (modeled as varying reward magnitude ratios) and different modalities of "choice cost" (modeled as either increasing repetitive motor output to obtain reward or increased delay to reward delivery). We demonstrate that (1) mouse choice is highly sensitive to the relative benefit of outcomes; (2) choice costs are heavily discounted in environments with large discrepancies in relative reward; (3) divergent cost modalities are differentially integrated into action selection; (4) individual mouse sensitivity to reward benefit is correlated with sensitivity to reward costs. These paradigms reveal stable individual animal differences in value-based action selection, thereby providing a foundation for interrogating the neural circuit and molecular pathophysiology of goal-directed dysfunction.