这项研究是由赠款R01-MH090127，P30-MH089868从心理健康国家研究所和获奖数量UL1TR001120从国家中心推进转化科学的支持。内容完全是作者的责任，并不一定代表NIMH或NCATS的官方意见。此外，我们想衷心感谢大卫Morilak博士为他宝贵的专业知识指导早期方法开发。

注意:在此研究中使用的动物是4和6个月的年龄以获得最佳效果之间雄性C57BL / 6J小鼠。小鼠保持在反向光周期，以便在活动（暗）相方便对它们进行测试。如果在一个房间分开壳体被执行的行为，小鼠被允许至少1小时，以适应下列运送到测试室。下红光条件下进行行为测试尽量减少对小鼠尽可能少的正常活动，同时仍然允许实验者足够的照明，以在视觉上监视测试会话。 注:这里所描述的实验过程的各个方面，进行了符合指南实验动物的护理和使用，第8版（NRC）和得克萨斯健康科学大学被批准的机构动物护理和使用委员会中心在圣安东尼奥。 <ol><li>填充陶瓷ramekins（非多孔性; 1.5"深×2.5"直径），至内缘与（约1挖掘介质"从底部）;滤纸轮切成两半，并贴在里面ramekin的背面（ 图1A） </li><li>打破轻轻加糖干早餐谷物（食物奖励） - 蜂蜜坚果或糖衣品种，为大约20毫克的片断为适应环境，培训和测试阶段。 </li><li>做一个注意力集中转移任务（AST）室（ 图1B）:驯化训练和测试每个鼠标在小室;建议至少为8腔室的生产。 <ol><li>建立一个12"×8"×7"AST室;墙壁和起点门制成的不透明的白色丙烯酸类，很容易清洗，用70％的乙醇。断头台式，可移动的起跑线分离室到等候区（5"×8"）和测试区（7"×8"）。 </li><li>包括明确5221; X7"可移动隔板分隔试验区均匀的两面;切3¼"直径的孔进入分区的底部部分，以允许访问嗅的，间隔1"从分区（ 图1C）的前面相距和1"。 </li></ol></li></ol> 2.步骤概述（图2） <ol><li>之前的AST，家鼠单独和允许他们调整到反向光周期为至少一周。 </li><li>适应，训练和测试单独测试室的每个动物。整理测试的最后一天后分配每个室一个鼠标和干净，用70％的乙醇。这将通过使室内的气味像"家笼"或"自我"测试期间尽量减少压力。 </li><li>气味测试盆前2天的测试，让气味消散;老鼠不会挖有一个非常强烈的气味盆。使用与地下25针的注射器，加入大约0.1毫升精油在滤纸的顶部。 </li></ol> 3.处理（1-8天） <ol><li>手柄起动之前，限食的第一天8天小鼠。这将减少与在测试过程中的处理相关的应力。 </li><li>权衡和处理记录体重每一天。每天处理每只小鼠2-3分钟。 </li><li>如果有多个实验者要参与测试的一组老鼠，确保每个参与实验者在搬运过程中增加熟悉实验者，降低压力和焦虑有经验的培训或测试天。 </li><li>继续处理和记录的权重整个测试的持续时间。 </li></ol> 4.食品的限制（9-12天） <ol><li>开始驯化的入门4天前，地方小鼠限制饮食来维持小鼠在他们的自由喂养体重的80-85％。给1克每只小鼠每天的食物。如果低于体重下降指定范围内的给每天2克直至它们返回到适当的范围内。 </li><li>放置2 ramekins在每个笼子的前面，以允许小鼠适应环境到测试盆。这是用来训练鼠标挖食物奖励相同点。 </li><li>添加在ramekins2克食品和1片食物奖励（半片谷物中的每一个）中的每一天为4天。 </li><li>如果行为是在一个单独的房间比1，其中将小鼠收容执行，开始对食物限制1日之前，运输小鼠在试验室，每天至少1小时返回到容纳室，以允许他们适应的检验室。 </li><li>在限食的最后一天，驯化开始前，更改家庭笼的床上用品。笼子里的床上用品将不会再改变，直到测试后完成，以减少在训练和测试（除非绝对必要），压力或焦虑体验。 </li><li>维持小鼠食物限制，直到测试结束。在13-17天，根据食物奖励的消耗（一般&lt;1克食物颗粒）的量的估计驯化，培训或测试后，给老鼠的食物。 </li></ol> 5.驯化（13-14天） <ol><li>开始训练开始前2天，在红​​光下黑暗周期中进行驯化。 </li><li>散布少量脏寝具从腔室中的家笼中，这将通过引入一个熟悉的"家笼"或"自"闻到测试腔室减少在新环境中作为应力（同一腔室将用于单一鼠标的训练和测试）的持续时间。 </li><li>放置一个干净ramekin与水在腔室的等候区;小鼠倾向于不进食，如果他们没有获得水。 </li><li>放置已用于食品限制在测试区域与食物奖励两个ramekins（〜20毫克谷物片）的每一个。 </li><li>鼠标放置在等候区;取出起点门并允许小鼠探索室1小时。 </li><li>不断以鼓励老鼠探索试验区，并经常在盆添加食物奖励（约20毫克谷物片）为空ramekins。 </li><li>确保鼠标可以看到实验者在整个适应期，使实验者的存在不是在测试过程中一个额外的压力源。 </li></ol> 6.培训（15日） <ol><li>鼠标放置在等候区。 </li><li>放置空ramekins，各含有食物奖励（〜20毫克谷物片），进入测试区和解除起点门。让鼠标3分钟检索两种食物奖励。重复此步骤几次。 </li><li> 逐步添加锯末/鼠笼床上用品在随后的试验盆。允许小鼠3分钟结束三正之前检索从每个罐的食物奖励人。一旦鼠标已经检索到的食物奖励从每个锅，继续下试。如果鼠标完全不挖，一旦食物奖励部分覆盖做出尝试，提示可以提供（ 即，撒上谷物粉尘在食物奖励的面积，使锯末了食物奖励的区域中的凹痕，发现部分食物奖励）。 </li><li>继续每次试验后，加入木屑/床上用品，直到食物奖励被完全覆盖和鼠标可靠演示了一个满钵挖找食物奖励的能力。 </li><li>如果鼠标还没有可靠地证明发现在2小时的训练开始的在一个完整的锅食物奖励的能力，继续培养第二日。保持鼠标的食物限制，重复此步骤的第二天。 </li><li>如果鼠标无法挖掘后连续两天食物奖励，从实验的剩余部分排除，并标注为"失败挖"的EXPerimental记录。 </li></ol> 7.测试（16-17天）: <ol><li>在一天之内，测试简单的辨别（SD），复合歧视（CD），反转（R1）和内维移（IDS）。 </li><li>在为期两天，测试内部维2班（IDS2），内维班3（IDS3），逆转2（R2;可选），额外的维移（EDS）。 </li><li>对媒体和香料如表1所示。 </li><li>在操控性上测试一天时间，给小鼠一种食物奖励，以避免缺乏焦点在测试过程中，由于饥饿。从这点开始直至测试日结束时，不除外正确选择奖励提供任何食物。 </li><li>在测试开始时，使用镊子（限制盆之间的气味蔓延）将一块在锅内，指示正确选择食物奖励。食物奖励应完全由媒体（参见图3）。为了避免从食物奖励气味线索，撒上谷物粉尘Ø版本的所有盆的阶段的开始。 </li><li>鼠标放置在等候区与起点门关闭。将盆在测试腔室的任一侧。当起点门被去除，计时器被启动试用开始。允许每个审判每只小鼠3分钟做出选择。记录的选择（正确或不正确），并时间直到鼠标制成每次试验一的选择。 注:"选择"是企图在任一火锅挖表示。挖苦只记录为选择，如果鼠标已经取代了媒体和戳它的鼻子远远不够的空间它创建找食物奖励的媒体或移位足以揭开食物奖励。如果鼠标没有在3分钟内做出了选择，这是记录为没有选择（不正确）。 </li><li>一旦选择已经取得了无论是火锅，删除未从测试室选择了锅。如果一个正确的选择作出，让鼠标将鼠标早在之前完成的食物奖励等候区。如果不正确的做出选择，让鼠标探索锅表明，没有食物奖励为选择鼠标回到等候区之前。 </li><li>在每次试验结束时，将鼠标早在等候区和替换起点门。 </li><li>确保鼠标满足8正确试验的标准连续前进到AST的下一个阶段。如果鼠标没有在50次试验获得8个正确的选择，连续，失败的阶段，不能移动到完成测试。连续6无选择（3分钟无选择）是失败的参与，并从上移动到下一个阶段禁止鼠标。 </li></ol>

<ol>
	<li>Birrell, J. M., Brown, V. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medial+frontal+cortex+mediates+perceptual+attentional+set+shifting+in+the+rat.">Medial frontal cortex mediates perceptual attentional set shifting in the rat.</a> J Neurosci. 20 (11), 4320-4324 (2000).</li><li>Garner, J. P., Thogerson, C. M., Wurbel, H., Murray, J. D., Mench, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+neuropsychology:+validation+of+the+Intra-Dimensional+Extra-Dimensional+set+shifting+task+for+mice.">Animal neuropsychology: validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice.</a> Behav Brain Res. 173 (1), 53-61 (2006).</li><li>Nagahara, A. H., Bernot, T., Tuszynski, M. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-related+cognitive+deficits+in+rhesus+monkeys+mirror+human+deficits+on+an+automated+test+battery.">Age-related cognitive deficits in rhesus monkeys mirror human deficits on an automated test battery.</a> Neurobiol Aging. 31 (6), 1020-1031 (2010).</li><li>Rock, P. L., Roiser, J. P., Riedel, W. J., Blackwell, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+impairment+in+depression:+a+systematic+review+and+meta-analysis.">Cognitive impairment in depression: a systematic review and meta-analysis.</a> Psychol Med. , 1-12 (2013).</li><li>Stuss, D. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Wisconsin+Card+Sorting+Test+performance+in+patients+with+focal+frontal+and+posterior+brain+damage:+effects+of+lesion+location+and+test+structure+on+separable+cognitive+processes.">Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes.</a> Neuropsychologia. 38 (4), 388-402 (2000).</li><li>Bissonette, G. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Double+dissociation+of+the+effects+of+medial+and+orbital+prefrontal+cortical+lesions+on+attentional+and+affective+shifts+in+mice.">Double dissociation of the effects of medial and orbital prefrontal cortical lesions on attentional and affective shifts in mice.</a> J Neurosci. 28 (44), 11124-11130 (2008).</li><li>Chase, E. A., Tait, D. S., Brown, V. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lesions+of+the+orbital+prefrontal+cortex+impair+the+formation+of+attentional+set+in+rats.">Lesions of the orbital prefrontal cortex impair the formation of attentional set in rats.</a> Eur J Neurosci. 36 (3), 2368-2375 (2012).</li><li>McAlonan, K., Brown, V. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Orbital+prefrontal+cortex+mediates+reversal+learning+and+not+attentional+set+shifting+in+the+rat.">Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat.</a> Behav Brain Res. 146 (1-2), 97-103 (2003).</li><li>Dias, R., Robbins, T. W., Roberts, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Primate+analogue+of+the+Wisconsin+Card+Sorting+Test:+effects+of+excitotoxic+lesions+of+the+prefrontal+cortex+in+the+marmoset.">Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset.</a> Behav Neurosci. 110 (5), 872-886 (1996).</li><li>Bissonette, G. B., Powell, E. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversal+learning+and+attentional+set-shifting+in+mice.">Reversal learning and attentional set-shifting in mice.</a> Neuropharmacology. 62 (3), 1168-1174 (2012).</li><li>Colacicco, G., Welzl, H., Lipp, H. P., Wurbel, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Attentional+set-shifting+in+mice:+modification+of+a+rat+paradigm,+and+evidence+for+strain-dependent+variation.">Attentional set-shifting in mice: modification of a rat paradigm, and evidence for strain-dependent variation.</a> Behav Brain Res. 132 (1), 95-102 (2002).</li><li>Kos, T., Nikiforuk, A., Rafa, D., Popik, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+NMDA+receptor+antagonists+on+attentional+set-shifting+task+performance+in+mice.">The effects of NMDA receptor antagonists on attentional set-shifting task performance in mice.</a> Psychopharmacology (Berl). 214 (4), 911-921 (2011).</li><li>Tait, D. S., Chase, E. A., Brown, V. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Attentional+Set-Shifting+in+Rodents:+a+Review+of+Behavioural+Methods+and+Pharmacological+Results.">Attentional Set-Shifting in Rodents: a Review of Behavioural Methods and Pharmacological Results.</a> Curr Pharm Des. , (2013).</li><li>Lapiz-Bluhm, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioural+assays+to+model+cognitive+and+affective+dimensions+of+depression+and+anxiety+in+rats.">Behavioural assays to model cognitive and affective dimensions of depression and anxiety in rats.</a> J Neuroendocrinol. 20 (10), 1115-1137 (2008).</li><li>Brigman, J. L., Bussey, T. J., Saksida, L. M., Rothblat, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Discrimination+of+multidimensional+visual+stimuli+by+mice:+intra-+and+extradimensional+shifts.">Discrimination of multidimensional visual stimuli by mice: intra- and extradimensional shifts.</a> Behav Neurosci. 119 (3), 839-842 (2005).</li></ol>

没有利益冲突的声明。

由PFC介导的在认知灵活性赤字表示与各种神经学和神经精神病学障碍有关的一个显著残疾，并且可以对结果和个人从这些疾病痛苦的生活质量产生重大的影响。在小鼠的AST使用的优化是研究遗传基础的连接到前额皮层介导的认知功能障碍的疾病至关重要。我们已发现，上述的方法是一个具体的认知缺陷，认知灵活性的可靠量度，并且近似于使用该任务在大鼠和非人灵长类动物中获得的结果。描述的方法是在大鼠和小鼠以及专家在我院的咨询和指​​导，前面描述的协议的广泛调查的结果。 使用在小鼠中类似的任务之前的报道已经证明这样的行为措施的适应性，尽管几个注意事项2,6,11。 Colacicco 等不限歧视每天进行测试，以2，该扩散测试在四天期间11的数量。这包括在连续测试天以前学过的刺激对重复。虽然有效，显影这里介绍的协议的目的是最大限度地减少测试期间的持续时间，最大限度地提高效率。在这里，我们限制测试，两天之内，消除了以前学过的刺激对重复。先前的研究人员指出，老鼠需要过度训练，形成一个集注意力和展览中，他们将保持付出努力应对一个小的"可测性的窗口"。我们的协议还包括在最初的相关线索维度中intradimensional转向适度的过度训练。评估在图4C的规范化的数据特别是当，似乎只小鼠中的协议检测可显示出更明显的赤字杜里纳克第二intradimensional反转（相对于前一阶段）。这个观察结果与过度训练，以确保形成一个所注意的组，如小鼠也表现出一个ID / ED移的概念相一致。一种可能性，为什么小鼠维持在我们的协议（ 图5），它涉及到2小时的平均会话长度付出努力的性能，可能是由于使用的反向光周期。我们在最初四小时黑暗（清醒）周期的测试，在红光下的照明条件下的隔离和专用的检测室的行为。然而，这种方法的手稿的范围之外的系统的测试将要求以确定哪些因素有助于在其中小鼠将继续执行的AST的持续时间，并且如果在嗅觉辨别缺陷的怀疑，预筛选可以在测试之前作为候补保证无异味的方法已有报道。 此外，在最初的方法开发中，我们发现，年轻的成年小鼠（8-12周龄）具有更大的可变性是年龄稍大的4-6个月大的老鼠进行。我们推测，食物限制协议影响生长的小鼠不同于更成熟的小鼠，并同时，在一个典型的神经发育意义上说，小鼠大脑被认为是完全由6周开发的，它有可能从青少年到成年人的成熟和成年早期的过渡在年轻小鼠的前额叶皮层变乱AST性能突触重塑。然而，这些迷人的问题仍有待探索。 在小鼠的AST协议的其他变型包括"自由"的试验，这意味着试验的指定数目（通常为4），在每一个阶段的开始不计分，并在动物被允许探索两者盆直至奖励被检索。在这里详细的协议不包括任何"免费"的试验。此外，我们设置了requiremeNTS以满足标准更严格（8连续正确试验，以标准，而不是先前描述的8/10试验，以满足标准），并已发现，这是其中的动物是否已真正了解到该规则的有效指标。加纳等。显示以下内容的IDS一段过度训练的（ 即呈现先前有关刺激额外50项试验）显著试验增加了EDS 2标准。在这里，我们包括多个帧内维位移，以努力"训练过度"，并确保一个所注意的集合的相关尺寸上的形成，在协议与Bissonette等人的。6。另外，加纳等。有限的测试会话，以约1小时（或当鼠标不再回应）2，而我们发现，C57BL6 / J小鼠充分且可靠地通过在大约2小时内每 ​​一天提交给他们的所有四个阶段进行（用于控制小鼠）。虽然，在实验组之间的运动能力电位差应该解释的性能时予以考虑。我们的手术限制的时间和劳动投入到17天的从处理通过完成测试开始每个动物。建议在一个单独的实验者限制在一个单一的一天受试小鼠的数目不超过2，其允许单个实验者完成测试在至少6的能力（这可以根据个人实验者的能力和经验被修改）小鼠每周。如果运动功能轻度受损，每次试验的长度可以增加，因为正确的响应，没有速度响应，是关键的因变量。 视觉辨别范式类似于那些已被用来评估认知表现在非人灵长类最近已适于在啮齿类动物中的使用，并且可以作为替代的气味和介质discriminatioñ这里描述的任务。这种方法可能是必要的，如果是本实验组小鼠之间在嗅觉辨别显著差异。 Brigman 等人已经表明，小鼠容易辨别化合物视觉刺激中的ID和ED移范例15。虽然这种自动化方法更好地表示在测试来研究在人类和非人类的灵长类动物前额叶皮层功能障碍，所需的操作室和触摸屏的成本来执行在小鼠中这个自动化测试可能是令人望而却步。 因此建议行为来对每个小鼠，也就是说 ，习惯化，训练尽可能一致执行并且测试应该在一天中的每个动物在同一时间进行。另外，动作室应在整个实验保持不变，使得利用共享/社区空间问题，由于不可控的流量，引入的气味等。如果动物是要传送从容纳室向远程行为的房间（如这里的情形），相同的路线应每次服用。行为室应在实验者和动物将不会在测试过程中被干扰的区域。如果多个实验者正在执行中，从房间内的同一个房间，进入和退出的任务，应尽可能限制，以避免任何过大噪声或中断可能在测试期间增加动物的压力或焦虑。另外，实验者应小心地除去和更换起点门以及盆流入和流出腔室的，以便产生尽可能少的噪声和干扰成为可能。大鼠进行的实验已经证明，AST性能可通过各种压力被打乱。 应每星期进行盆窨并在每个星期的同一天，前至少2天到第一测试日。它建议在盆香味在良好通气其中测试将被执行的范围的外侧ilated区域（如单独的实验室，走廊，通风柜）。这将有助于避免气味的交叉污染，并避免混淆小鼠气味不属于试验的一部分。此外，前和测试过程中，（ 即，胶或咖啡之前立即测试，强香料/除臭等消费）应避免上述的理由强的气味可以分散从鉴别动物。应实验者希望使用比在该协议中所述备用挖掘介质，建议该介质是相似的密度和重量，以在这里描述的（过度重量/密度使得难以为鼠标挖充分）的。例如，我们发现，小塑料珠是不合适的，因为它们是困难的小鼠推开。此外，具有很强的气味任何媒体（ 例如 ，橡胶带和一些PLASTIC材料）不适合，因为它可能与检测到的气味被测试的能力产生干扰。 训练和个体小鼠的测试应该由单个实验者来进行，但是适应可以通过任何实验者只要他们已经参加的处理完成。要使用在每一天所执行的四个阶段的所有盆应伸手可及以便限制的时间量的动物是在阶​​段之间的等候区。这将有助于保持鼠标放在每个任务的关注。此外，不要停止，直到完成的那一天的测试（ 即所有4个阶段对每个测试日必须连续完成）的任务，一旦测试开始是很重要的。 总之，这里所描述的协议提供了AST的有效利用来衡量前额叶皮质依赖的认知功能的影响，其中包括详细的说明方法说明数据分析和潜在的注意事项。多种小鼠的AST的方法报道于主文献，每个都有自己的独特的程序细节。无论基于文本和视觉信息的独特的耦合将特别有助于研究人员试图将这一强大的行为检测到他们的科学剧目。

在注意力集中转移任务（AST）前1,2是发展成为人们关注和认知弹性的大鼠了十多年。剑桥神经心理测试自动化电池（CANTAB），其被用于识别认知功能障碍的人类和非人类灵长类3,4的intradimensional /异次元分量后的AST被建模。同时学习简单的规则的能力保持不变，在学习赤字修改时，规则已经改变被发现在患者从各种神经精神障碍（如精神分裂症，强迫症，抑郁症）的痛苦，神经退行性疾病的响应（ 即，帕金森氏病）和患者的病灶，以预额叶皮层5。更一般地，这些患者被描述为具有在认知灵活性缺陷。类似的赤字在这两个非人类灵长类动物和啮齿动物时，病变吨被证明澳前额叶皮质已被诱导1,6-8。这些赤字表明认知僵化的状态或转移注意力集中的能力受损。 形成有注意力集当受试者得知的一组规则可应用于复杂的刺激，以从不相干线索分化有关。例如，在AST，动物将学习关注并给有关的提示（ 即，挖掘介质）响应，而忽略不相关的线索（ 即气味），通过配对食物奖励与介质。此关联随后在后续的任务，其中钢筋挖掘介质和气味的变化的类型，但介质和收益之间的配对关联保持。这种增强的规则形成了认知集。逆转和额外维的转变:在认知灵活性 AST协议的措施方面的两个阶段。在逆转的阶段，在一个dimensio先前负面刺激N（介质在本实施例）现在是肯定的，挑战动物忽略来自前一阶段的正面刺激。例如，如果感觉挖介质是在前一阶段的积极的刺激和纸是负的刺激，现在的情况正好相反。这种挑战，它必须保持注意力集中的动物的灵活性（ 即介质相关的尺寸），而改变规则，学会了一个维度内的刺激和奖励对。一个所注意的集合的形成在额外维移阶​​段，当不相关的维度（气味在这个例子中）成为相关的尺寸受到了挑战。一个固着的反应，通过使用以前学过的规则持续选择所示，在任一阶段，反映了认知灵活性的赤字。 在两个非人类灵长类动物和啮齿类动物损伤的研究显示前额叶皮层的特定区域可以归因于为PErF能力ORM的AST 1,9特定阶段。病变的眶额皮层（OFC），前额皮层（PFC）的次区域，已被证明是导致学习上的AST 8赤字逆转。此外，病变的内侧前额叶皮质（MPFC），导致在执行额外的维度转变的具体困难。 同时使用的AST许多研究在大鼠和非人灵长类动物被执行时，相对较少的已利用的AST如小鼠认知功能的量度。鉴于遗传操作的易用性小鼠，以及迫切需要测量前额叶皮质功能在研究各种障碍，适应和验证小鼠这种行为的措施是一个重要的除了研究与PFC功能障碍相关的疾病。这里详述的方案是由比勒尔和Brown 1被应用在小鼠中优化和过程的修改反映了许多小鼠- specifi的之前已经报道2,6,10-13Ç适应。

<table><tbody><tr><td>Testing Chamber</td><td></td><td></td><td>Fabricated in-house, specifications can be found in protocol</td></tr><tr><td>3 oz. Ramekins</td><td>BIA Cordon Bleu</td><td>900002S12</td><td>Purchased on amazon.com</td></tr><tr><td>Essential Oils:</td><td>Fronteir Natural Products Co-Op</td><td></td><td>Purchased on http://www.frontiercoop.com/prodlist.php?ct=anpceoeo</td></tr><tr><td>Clove Bud</td><td></td><td>191114</td><td></td></tr><tr><td>Red Thyme</td><td></td><td>191140</td><td></td></tr><tr><td>Lemon</td><td></td><td>190810</td><td></td></tr><tr><td>Cinnamon Leaf</td><td></td><td>191111</td><td></td></tr><tr><td>Rosemary</td><td></td><td>191133</td><td></td></tr><tr><td>Citronella Java</td><td></td><td>191112</td><td></td></tr><tr><td>Vanilla in jojoba oil</td><td></td><td>191231</td><td></td></tr><tr><td>Anise Seed</td><td></td><td>191102</td><td></td></tr><tr><td>Ginger</td><td></td><td>191121</td><td></td></tr><tr><td>Nutmeg</td><td></td><td>191161</td><td></td></tr><tr><td>Filter Paper, 9.0 cm diameter</td><td>VWR International</td><td>28310-048</td><td>Purchased on https://us.vwr.com/</td></tr><tr><td>Digging Media</td><td></td><td></td><td></td></tr><tr><td>Raffia</td><td>Ashland 8 oz Raffia</td><td></td><td>Purchased on http://www.michaels.com/&lt;br/&gt; Cut into 1/2&quot; to 1&quot; strips</td></tr><tr><td>Green Felt</td><td>Creatology Basic Felt Forest/Dark Green 36 in x 36 in&amp;nbsp;</td><td></td><td>Purchased on http://www.michaels.com/&lt;br/&gt; cut into 1 cm x 1 cm squares</td></tr><tr><td>Brown foam</td><td>Creatology Fun Foam 18 x 12 in sheets (light brown/tan)</td><td></td><td>Purchased on http://www.michaels.com/&lt;br/&gt; cut into 1/2 cm x 2 cm rectangles</td></tr><tr><td>Crepe paper (yellow)</td><td>Celebrate It Paper Crinkle 4 oz yellow jumbo</td><td></td><td>Purchased on http://www.michaels.com/&lt;br/&gt; Cut into 1/2&quot; to 1&quot; strips</td></tr><tr><td>Ribbon (turqoise)</td><td>Celebrate It Wide Ribbon 4 in x 10 yd 100% polyester&amp;nbsp;</td><td></td><td>Purchased on http://www.michaels.com/&lt;br/&gt; cut into 1 cm x 1 cm squares</td></tr><tr><td>Metallic&amp;nbsp;</td><td>Celebrate It Metallic Crinkle Gold 2 oz</td><td></td><td>Purchased on http://www.michaels.com/&lt;br/&gt; Cut into 1/2&quot; to 1&quot; strips</td></tr><tr><td>Googly Eyes, 4 mm</td><td></td><td>ME4144</td><td>Purchased on http://factorydirectcraft.com/index.php</td></tr><tr><td>Black Sequins, 3 mm</td><td></td><td>8780BK</td><td></td></tr><tr><td>Pink Pom Poms, 1/4 inch</td><td></td><td>1018221</td><td></td></tr><tr><td>Pipe Cleaners, red</td><td></td><td>108430</td><td></td></tr><tr><td>Bedding material/sawdust</td><td></td><td></td><td>Obtained from in-house animal resources</td></tr><tr><td>Timer</td><td>Control Company</td><td>5000</td><td>Purchased on http://www.control3.com/5000p.htm</td></tr><tr><td>Lightly sweetened dry breakfast cereal loops</td><td>HEB&amp;nbsp;</td><td></td><td>Honey nut toasted oats used in the protocol described, any lightly sweet coated breakfast cereal is recommended</td></tr></tbody></table>

the attentional set shifting task: a measure of cognitive flexibility in mice

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain&#160;to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.

在该试验中，典型的从属措施是每阶段试验，以满足标准（或8个连续正确选择）的数目。 图4A示出试验的平均数来满足准则时使用的AST在未处理的C57BL / 6J每个阶段。小鼠形成对相关线索尺寸（气味或介质）的注意力集中，性能将提高，通过在试验的减少所指示，以满足标准的连续intradimensional移位的，并且反转阶段和异次元移将需要额外的试验，以满足标准。它以抗衡开头上每两个相关尺寸（ 即，媒体或气味），因为我们已经观察到一些差异，在简单的判别阶段反映在试验数量的增加，以标准如果气味是有关动物的数量是非常重要的线索（ 图4B）。如果试验，在SD阶段达到的标准是日之间显著不同E两个相关提示尺寸（ 即，更好的性能，当媒体有关， 如图4B），在随后的阶段，每个鼠标的性能数据，可以在简单的判别阶段归其性能。 如图4C所示 ，该归一化步骤降低了与学习的初始相关线索相关联的变异性并增强了对后续的IDS阶段改进的性能可视化。虽然〜20只小鼠的组大小将足以允许原始数据的分析，而无需正常化。重要的是，在试验中一个显著增加extradimentional移相对于以前intradimentional移指示中满足的标准是试验有效性（ 图4D和4E）的一个重要的控制措施。在此之前的ED变速级，小鼠学习，以找到该奖励注意单个相关线索尺寸（气味或介质）。切换到一个NE瓦特相关提示尺寸，这在以前无关，应该需要更多的试验，达到标准，导致ID / ED转变。有趣的是，在原始数据中的ID / ED移的分析显示，在试验中一个显著增加IDS2和ED（ 图4D）之间达到标准，趋势朝着增加IDS3和ED之间（数据未示出，P &lt;0.1）并增加了平均试验间相比ED（数据未示出），以达到IDS2和IDS3的标准。有趣的是，一个显著ID / ED换档既IDS2和IDS3之间表观相比ED时该数据标准化为表现在在SD阶段（ 图4E）。 据预计，对照小鼠的约70％-80％将完成整个任务（20-30％退出率）。替代相关措施包括平均延迟为在任务的每个阶段衡量做出选择（虽然我们已经发现这是老鼠之间差异很大），通过Lapiz-Bluhm的等 14如以下三个或更多个连续正确选择次数的不正确的选择作出的数目所定义的错误"设置损失"的反转和错误的额外维变速级和数目的总数。 "集丢失"的错误数量的增加可能表明固着行为。此外，小鼠通常完成测试的每一个阶段，在不到30分钟（ 图5），和时间在每个阶段所花费的持续时间是试验的函数，以达到标准。 在使用详见这里，神经病变的OFC或mPFC的小鼠类似的模式先前的研究中均表现分别影响性能的逆转和额外维的转变阶段，确认使用这个测试来确定功能缺损的相同的区域的大鼠和非人灵长类动物studies11。虽然任务在上述研究中诉序列白羊略到这里示出，但预计病变或缺陷在OFC和mPFC的同时也会导致性能受损在R 1和EDS，通过增加试验次数反映到标准在这些阶段。 。 <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td > 舞台 </td><td > 相应 </td><td colspan="2" > 示例 </td><td > 相应 </td><td > 示例 </td><td ></td></tr><tr><td >简单的歧视（SD） </td><td > 中 </td><td > 毡（+） </td><td >纸（ - ） </td><td > 气味 </td><td > 肉豆蔻（+） </td><td >迷迭香（ - ） </td></tr><tr><td rowspan="2">复方歧视（CD） </td><td > 中 </td><td > 毛毡（+）/肉豆蔻</td><td >纸（ - ）/迷迭香</td><td > 气味 </td><td > 肉豆蔻（+）/费尔特</td><td >迷迭香（ - ）/纸</td></tr><tr><td></td><td > 毛毡（+）/迷迭香</td><td >纸（ - ）/肉豆蔻</td><td></td><td > 肉豆蔻（+）/纸</td><td >迷迭香（ - ）/费尔特</td></tr><tr><td rowspan="2">逆转1（R 1） </td><td > 中 </td><td > 纸（+）/迷迭香</td><td >毡（ - ）/肉豆蔻</td><td > 气味 </td><td > 迷迭香（+）/纸</td><td >肉豆蔻（ - ）/费尔特</td></tr><tr><td></td><td > 纸（+）/肉豆蔻</td><td >毛毡（ - ）/迷迭香</td><td></td><td > 迷迭香（+）/费尔特</td><td >肉豆蔻（ - ）/纸</td></tr><tr><td rowspan="3"> Intradimensional移位（IDS） </td><td rowspan="2"> 中 </td><td > 绒球 </td><td rowspan="2">亮片（ - ）/丁香</td><td rowspan="2"> 气味 &lt;/ TD&gt; <td rowspan="2"> 肉桂（+）/绒球</td><td rowspan="2">丁香（ - ）/亮片</td></tr><tr><td > （+）/肉桂</td></tr><tr><td></td><td > 绒球（+）/丁香</td><td >亮片（ - ）/肉桂</td><td></td><td > 肉桂（+）/亮片</td><td >丁香（ - ）/绒球</td></tr><tr><td rowspan="3"> IDS2 </td><td rowspan="2"> 中 </td><td > Pipecleaners </td><td rowspan="2">曲棍球的眼睛（ - ）/姜</td><td rowspan="2"> 气味 </td><td rowspan="2"> 红色百里香（+）/ Pipecleaners </td><td rowspan="2">姜（ - ）/曲棍球眼睛</td></tr><tr><td > （+）/红百里香</td></tr><tr><td></td><td > Pipecleaners（+）/姜</td><td >曲棍球的眼睛（ - ）/红百里香</td><td></td><td > 红色百里香（+）/曲棍球眼睛</td><td > 姜（ - ） </STRONG&gt; / Pipecleaners </td></tr><tr><td rowspan="2"> IDS3 </td><td > 中 </td><td > 丝带（+）/香草</td><td >金属带（ - ）/柠檬</td><td > 气味 </td><td > 香草（+）/丝带</td><td >柠檬（ - ）/金属条</td></tr><tr><td></td><td > 丝带（+）/柠檬</td><td >金属带（ - ）/香草</td><td></td><td > 香草（+）/金属条</td><td >柠檬（ - ）/丝带</td></tr><tr><td rowspan="2"> R2 </td><td > 中 </td><td > 金属带（+）/香草</td><td >丝带（ - ）/柠檬</td><td > 气味 </td><td > 柠檬（+）/丝带</td><td >香草（ - ）/金属条</td></tr><tr><td></td><td > 金属带（+）/柠檬</td><td >丝带（ - ）/香草</td><td></td><td > 柠檬（+）/金属<html> LIC条</td><td >香草（ - ）/丝带</td></tr><tr><td rowspan="2">异次元移位（EDS） </td><td > 气味 </td><td > 香茅（+）/拉菲亚</td><td >八角（ - ）/泡沫</td><td > 中 </td><td > 拉菲亚（+）/香茅</td><td >泡沫（ - ）/大茴香</td></tr><tr><td></td><td > 香茅（+）/泡沫</td><td >大茴香（ - ）/拉菲亚</td><td></td><td > 拉菲亚（+）/大茴香</td><td >泡沫（ - ）/香茅</td></tr></tbody></table> 气味和挖掘介质的表1中。实施例组合的气味和挖介质中这些组合在本研究中已被证实。使用这些特定组合得到的代表性结果示于图2中 。 hres.jpg"/&gt; 图1. AST测试室。 （A）的照片和ramekin和举例的滤纸放置的尺寸。（B）的图片适于小鼠和（C）的测试室表示该分区中的孔放置的三维图AST的测试腔室的。 <img alt="图2" src="/files/ftp_upload/51944/51944fig2highres.jpg" /> 图2.挖掘中 。挖这个协议在材料清单（ii.-xi.）详细的使用中对例子。盆充满大致与挖介质内缘。 <img alt="图3" src="/files/ftp_upload/51944/51944fig3highres.jpg" /> 图3.时间轴进行测试。 <img alt="图4"SRC ="/文件/ ftp_upload / 51944 / 51944fig4highres.jpg"/&gt; 图4. C57BL / 6J性能中的AST。 （A）试验的平均次数，以满足标准的AST男性C57BL / 6J小鼠。数据表示平均值±SEM（N = 22只/组），P = 0.013舞台的重要作用。（B）试验的平均次数在SD阶段不同的初始相关提示尺寸达到标准。数据表示平均值±SEM（N = 22只/组），* p = 0.01。（C）标准化表示为每个鼠标的个性化表现在SD阶段的百分比数据。数据表示平均值±SEM（N = 22只/组），P = 0.06的阶段主要作用。（D）在试验ID / ED转向IDS2与ED之间达到标准。数据表示平均值±SEM（N = 22只/组），* p = 0.03。（E）ID / ED在IDS3与ED之间的标准化数据移位。数据表示平均值±SEM（N = 22只/组），* P = 0.012。

Watch this Scientific Journal Video about The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice at JoVE.com

The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

该协议的目的是为了执行行为分析，如注意力集转移任务（AST），以评估在小鼠中前额叶皮层介导的认知灵活性。

在注意定势转移任务:测量小鼠认知的灵活性

Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many ...

the-attentional-set-shifting-task-measure-cognitive-flexibility

Nanyang Technological University

Research

JoVE Journal

Behavior

27.1K 次观看.  University of Texas Health Science Center at San Antonio. 该协议的目的是为了执行行为分析，如注意力集转移任务（AST），以评估在小鼠中前额叶皮层介导的认知灵活性。 

视频: The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

一致性的任务作为一种手段来获取目标行为的措施中的橡胶手错觉范式Crossmodal

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

科研

行为学

The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, modifications to the standard task, can be used to systematically tax the neural systems controlling either attention or impulse control. Importantly, these challenges have consistent effects on behavior across laboratories in intact animals and can reveal either enhancements or deficits in cognitive function that are not apparent when rats are only tested on the standard task. The variety of behavioral measures that are collected can be used to determine if other factors (i.e., sedation, motivation deficits, locomotor impairments) are contributing to changes in performance. The versatility of the 5CSRTT is further enhanced because it is amenable to combination with pharmacological, molecular, and genetic techniques.

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, which are modifications of the standard task, increase flexibility of the task and can be combined with other manipulations to more fully characterize behavior.

5选择序列反应时任务：注意的任务和脉冲控制鼠害

This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. ...

A Dual Task Procedure Combined with Rapid Serial Visual Presentation to Test Attentional Blink for Nontargets

When viewers search for targets in a rapid serial visual presentation (RSVP) stream, if two targets are presented within about 500 msec of each other, the first target may be easy to spot but the second is likely to be missed. This phenomenon of attentional blink (AB) has been widely studied to probe the temporal capacity of attention for detecting visual targets. However, with the typical procedure of AB experiments, it is not possible to examine how the processing of non-target items in RSVP may be affected by attention. This paper describes a novel dual task procedure combined with RSVP to test effects of AB for nontargets at varied stimulus onset asynchronies (SOAs). In an exemplar experiment, a target category was first displayed, followed by a sequence of 8 nouns. If one of the nouns belonged to the target category, participants would respond &#8216;yes&#8217; at the end of the sequence, otherwise participants would respond &#8216;no&#8217;. Two 2-alternative forced choice memory tasks followed the response to determine if participants remembered the words immediately before or after the target, as well as a random word from another part of the sequence. In a second exemplar experiment, the same design was used, except that 1) the memory task was counterbalanced into two groups with SOAs of either 120 or 240 msec and 2) three memory tasks followed the sequence and tested remembrance for nontarget nouns in the sequence that could be anywhere from 3 items prior the target noun position to 3 items following the target noun position. Representative results from a previously published study demonstrate that our procedure can be used to examine divergent effects of attention that not only enhance targets but also suppress nontargets. Here we show results from a representative participant that replicated the previous finding.&#160;

This paper describes a novel dual task procedure combined with Rapid Serial Visual Presentation to look at attentional blink at varied stimulus onset asynchronies. This experimental procedure differed from others in that it tested attentional blink for nontargets.

的双任务过程结合快速系列视觉呈现到测试的注意闪烁Nontargets

When viewers search for targets in a rapid serial visual presentation (RSVP) stream, if two targets are presented within about 500 msec of each other, the ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

操作性程序，以评估大鼠的行为灵活性

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

An Operant Intra-/Extra-dimensional Set-shift Task for Mice

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric diseases. The most widely used neuropsychological tests for the evaluation of attentional set-shifting in human subjects are the Wisconsin Card Sorting Test (WCST) and the CANTAB Intra-/Extra-dimensional set shift task (ID/ED). These tasks have proven clinical relevance and have been modified and successfully adapted for research in animal models. However, currently available tasks for rodents present several limitations, mainly due to their manual-based testing procedures, which are hampering translational advances in psychiatric medicine. To overcome these limitations and to better mimic the original version in primates, we present the development of a novel operant-based two-chamber ID/ED "Operon" task for rodents. We demonstrated the effectiveness of this novel task to measure different facets of cognitive flexibility in mice including attentional set formation and shifting, and reversal learning. Moreover, we show the high flexibility of this task in which three different perceptual dimensions can be manipulated with a high number of stimuli cues for each dimension. This novel ID/ED Operon task can be an effective preclinical tool for drug testing and/or large genetic screening relevant to the study of executive dysfunction and cognitive symptoms found in psychiatric disorders.

Attentional set-shifting cognitive abnormalities are a core feature of many psychiatric diseases. Here, we present the development of a novel automatic system for the effective study of attentional set-shifting abilities, executive functions and other cognitive abilities in mice with high translational validity to human studies.

一个操作性内/外维特班任务的小鼠

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric ...

The Emotional Stroop Task: Assessing Cognitive Performance under Exposure to Emotional Content

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The difference shows that people are affected by the emotional content conveyed by the carrier words even though they are irrelevant to the color-naming task at hand. The ESE has been widely deployed with patient populations, as well as with non-selected populations, because the emotion words can be selected to match the tested pathology. The ESE is a powerful tool, yet it is vulnerable to various threats to its validity. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them. The most prevalent threat to the validity of existing ESE studies is sustained effects and habituation wrought about by repeated exposure to emotion stimuli. Consequently, the order of exposure to emotion and neutral stimuli is of utmost importance. We show that in the standard design, only one specific order produces the ESE.

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than those of neutral words. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them.

情绪Stroop任务:评估下暴露的认知表现的情感内容

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The ...

New Variations for Strategy Set-shifting in the Rat

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy based on a change in governing rules. We describe a strategy set-shifting task that requires an attentional shift from one stimulus dimension to another. The paradigm is often used for testing cognitive flexibility in primates. However, the rodent version has not been as extensively developed. We have recently extended an established set-shifting task in the rat1 by requiring attention to different stimuli according to context. All the experimental conditions required animals to choose either a left or right lever. Initially, all animals had to choose on the basis of the location of the lever. Subsequently, a change in the rule occurred, which required a shift in set from location-based rule to a rule in which the correct lever was indicated by a light cue. We compared performance on three different versions of the task, in which the light stimulus was either novel, previously relevant, or previously irrelevant. We found that specific neurochemical lesions selectively impaired the ability to make particular types of set shift as measured by the performance on the different versions of the task.

Set-shifting, a form of behavioral flexibility, requires an attentional shift from one stimulus dimension to another. We extended an established rodent set-shifting task1 by requiring attention to different stimuli according to context. The task was combined with specific lesions to identify neuron subtypes underlying a successful shift.

对于战略的新变化集移在大鼠

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy ...

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of &alpha;-CaMKII+/- mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that &alpha;-CaMKII+/- mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that &alpha;-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.

This article presents the protocol of T-maze tests using a modified automated apparatus for assessing the learning and memory functions in mice.

T-迷宫强迫交替和评估工作，并参考在小鼠记忆的左，右的歧视任务

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in ...

神经科学

Assessment of Stress Effects on Cognitive Flexibility using an Operant Strategy Shifting Paradigm

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and duration of the stressor; 2) type of cognitive function under study; and 3) timing of the stressor in relation to learning or executing the cognitive task. Furthermore, sex differences among the effects of stress on cognitive function have been widely documented. Described here is an adaptation of an automated operant strategy shifting paradigm to assess how variations in stress affect cognitive flexibility in male and female Sprague Dawley rats. Specifically, restraint stress is used before or after training in this operant-based task to examine how stress affects cognitive performance in both sexes. Particular brain areas associated with each task in this automated paradigm have been well-established (i.e., the medial prefrontal cortex and orbitofrontal cortex). This allows for targeted manipulations during the experiment or the assessment of particular genes and proteins in these regions upon completion of the paradigm. This paradigm also allows for the detection of different types of performance errors that occur after stress, each of which has defined neural substrates. Also identified are distinct sex differences in perseverative errors after a repeated restraint stress paradigm. The use of these techniques in a preclinical model may reveal how stress affects the brain and impairs cognition in psychiatric disorders, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), which display marked sex differences in prevalence.

Stressful life events impair cognitive function, increasing the risk of psychiatric disorders. This protocol illustrates how stress affects cognitive flexibility using an automated operant strategy shifting paradigm in male and female Sprague Dawley rats. Specific brain areas underlying particular behaviors are discussed, and translational relevance of results are explored.

使用操作策略转移范式评估压力对认知灵活性的影响

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and ...

Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that measures motivation to expend effort and obtain reward. In mice, chronic stress exposure significantly impacts motivation to work for a higher value reward when a lesser value reward is freely available compared to unstressed mice. Here we describe the chronic corticosterone administration paradigm, which produces a shift in effortful responding in the Y-maze barrier task. In the Y-maze task, one arm contains 4 food pellets, while the other arm contains only 2 pellets. After mice learn to select the high reward arm, barriers with progressively increasing height are then introduced into the high reward arm over multiple test sessions. Unfortunately, most chronic stress paradigms (including corticosterone and social defeat) were developed in male mice and are less effective in female mice. Therefore, we also discuss chronic non-discriminatory social defeat stress (CNSDS), a stress paradigm we developed that is effective in both male and female mice. Repeating results with multiple distinct chronic stressors in male and female mice combined with increased usage of translationally relevant behavior tasks will help to advance the understanding of how chronic stress can precipitate mood disorders.

The Y-maze barrier task is a behavior test that examines motivation to expend effort for reward. Here, we discuss testing multiple well-validated chronic stressors including chronic corticosterone and social defeat stress with this behavior, as well as the novel chronic non-discriminatory social defeat stress (CNSDS), which is effective in females.

在小鼠的 Y-Maze 障碍任务中，慢性应力转移与工作量相关的选择行为

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that ...