Kalajzic Katarina, Stout John J, Mitchell Alexander C, Spellman Timothy
Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA.
Bio Protoc. 2025 Sep 5;15(17):e5442. doi: 10.21769/BioProtoc.5442.
Cognitive flexibility is a process that involves dynamically adapting behavior to obtain a desired series of outcomes during continuously changing stimulus-response-reward associations. Attentional set-shifting is a multi-modal decision-making paradigm that tests cognitive flexibility, which can be useful for investigating neural circuitry that is disrupted in multiple neuropsychiatric disorders, including schizophrenia, Alzheimer's disease, depression, and addiction. The canonical human attentional set-shifting paradigm for measuring cognitive flexibility is the Wisconsin Card Sorting Test, in which subjects sort cards based on rules that change periodically and adapt their behavior by utilizing feedback in the form of correct and incorrect outcomes. To transfer these tests to rodent models, previous techniques involved attentional set-shifting paradigms in free-roaming test chambers, in which animals associated cues with reward locations. The protocol presented here involves an analogous attentional set-shifting paradigm, in which water-restricted mice are head-restrained on a platform and must keep track of periodically switching stimulus-response-outcome associations. The mice must learn to associate odor or whisker vibration cues with a binary directional lick response that triggers water delivery. The mice are trained to respond by licking one of two spouts, in which the correct decision is dependent on the current stimulus rule. This protocol allows for behaviorally measuring cognitive flexibility alongside neural activity by pairing the head-restrained paradigm with 2-photon calcium imaging, optogenetics, and extracellular and intracellular physiology. Key features • Head-restraint design that allows for optogenetic manipulation, in vivo imaging, extracellular and intracellular electrophysiology, and other manipulations. • Attentional set-shifting paradigm that measures cognitive flexibility in rodents.
认知灵活性是一个过程，涉及在不断变化的刺激-反应-奖励关联中动态调整行为，以获得一系列期望的结果。注意力转换是一种多模态决策范式，用于测试认知灵活性，这对于研究在多种神经精神疾病（包括精神分裂症、阿尔茨海默病、抑郁症和成瘾症）中受到破坏的神经回路很有用。用于测量认知灵活性的经典人类注意力转换范式是威斯康星卡片分类测试，在该测试中，受试者根据定期变化的规则对卡片进行分类，并通过利用正确和错误结果形式的反馈来调整他们的行为。为了将这些测试转移到啮齿动物模型中，以前的技术涉及在自由活动的测试箱中的注意力转换范式，在这种范式中，动物将线索与奖励位置联系起来。这里介绍的方案涉及一种类似的注意力转换范式，在该范式中，限水的小鼠被头部固定在一个平台上，并且必须跟踪定期切换的刺激-反应-结果关联。小鼠必须学会将气味或胡须振动线索与触发水供应的二元方向舔舐反应联系起来。小鼠被训练通过舔舐两个喷嘴之一来做出反应，其中正确的决定取决于当前的刺激规则。该方案通过将头部固定范式与双光子钙成像、光遗传学以及细胞外和细胞内生理学相结合，允许在行为上测量认知灵活性以及神经活动。关键特征 • 允许进行光遗传学操作、体内成像、细胞外和细胞内电生理学以及其他操作的头部固定设计。 • 测量啮齿动物认知灵活性的注意力转换范式。
