This study was supported by Human Frontier Science Program and the Sasakawa Scientific Research Grant from the Japan Science Society.

使用动物的所有的程序是由动物护理和使用委员会在科学和技术研究所冲绳批准。 1.动物<ol><li>获得男Long-Evans大鼠（250-300克，以到达）。 </li><li>抵达后，房子一组两个或三个老鼠在一起一个星期，后来他们分成单独的笼子里。请注意，这个实验设计涉及到食品的限制，需要在每个网箱控制消耗的食物保存的动物。 </li><li>提供食物和水随意所有动物，并在标准条件下容纳他们（12小时/ 12小时亮/暗循环，在23℃）。 </li><li>行为实验开始前5天，用自由饮水整个实验食动物限制在大约其平均体重的85％。 </li><li>处理的动物每天5分钟进行的实验开始前至少5天，以了解吨与实验者下摆。 </li></ol> 2.硬件和软件的行为测试和分析<ol><li> 硬件 <ol><li>使用配有消音框中操作性室。 </li><li>该室被掺入几个附加的附件:二容器杆在前面板上，两个光暗示，杠杆之上，一本杂志斑点有用于检测两个杆之间头条目，一个食品分配器，一个纯音发生器和一个传感器后面板上的房子光。 </li></ol></li><li> 软件 <ol><li>控制下的所有反式IV软件编写的编程代码的行为事件。使用医学-PC IV软件信号和检测所有的培训和测试过程中的行为事件。 </li><li>使用反式IV为行为测试编写代码。打开一个新的文件进行写入。 </li><li>一旦程序编写，翻译和软件中进行编译。修改代码，如果错误检测和重试。 </li><li>一旦一个程序的调试成功，检查用户的代码工作正常通过进行实验实际开始前试运行。 </li><li>使用MED-PC IV，运行行为实验。打开软件，点击"打开会话"和一个程序分配给每个箱子。 </li><li>在所有的方案都被正确分配给每个箱子，送需要启动的实验信号。 </li><li>任务完成后，数据保存为单击"保存数据"，或写代码来自动保存数据（详见程序员的MED-PC IV手册）。 </li><li>一旦数据被导出到指定的文件夹，重命名为数据采集日期和动物的ID号码以备后用。所收集的数据导入matlab进行（协议3.7）以下所述的行为分析。 </li></ol></li></ol> 3.行为训练和测试<ol><li> 习惯和杂志的培训。 </STRONG&gt; <ol><li>这些阶段中目前还没有杠杆动物。 </li><li>在习惯阶段，将动物每天20分钟操作性室。就在同一天，给予10蔗糖颗粒（45毫克），动物在他们的家笼中，其中哪些熟悉的蔗糖奖励。 </li><li>接下来，开始训练的杂志。放置动物腔室，并给20蔗糖小丸（每一分钟1片）的动物，从而提供一个机会学习粒料的食物托盘和获取的位置。 注:这些阶段可以跳过由于对获得颗粒无操作反应的动物潜在的混乱，即使我们采用他们作出一个熟悉室和食物托盘食的动物。 </li></ol></li><li> 连续配筋时间表 <ol><li>列车连续强化程序的动物按杠杆来获取奖励。本次培训的会议将持续到60粒的蜜蜂n中的接收（60杆压力机）或40分钟是否已经过去。 </li><li>本要么整个会议（直至获得30粒）的前半部分的左侧或右侧杠杆，接着相对杆的呈现期间的第二半。的顺序是交替每天的基础上。 </li><li>这继续强化程序，直到动物已成功获得60的奖励至少连续2天。注意，可能存在的动物之间的高变异性，他们如何迅速使第一杆压，这可能会影响加固的进度。在这种情况下，把一个杠杆提出了一些蔗糖颗粒激励他们朝着无响应时已经取得了第一届杠杆接近。 注:一种可能的替代方案是将蔗糖小丸当杠杆首先提交给动物，以便使这个阶段的完成更快。 </li></ol></li><li> 在杠杆新闻培训和测试试验时间表。 </str翁&gt; <ol><li>开始一个3秒（S）音审单。 </li><li> 2秒音结束后，现在两个杠杆，让动物在10秒内按下任一杆。在没有响应10秒内作出的情况下，收回两个杠杆和计数这次审判为疏忽审判。 </li><li>在杠杆压训练，只存在于任一侧的单个杠杆的情况下。 </li><li>在大多数的实验条件下，有一个光刺激上述杠杆之一。打开乐音停止后，立即光球杆和关闭时的动物要么制成的反应或在杆插入后10秒无响应已取得时。 </li><li>在20〜30秒设定试验间的时间间隔。 </li></ol></li><li> 杠杆记者培训 <ol><li>在这个训练阶段，目前没有光线的动物。 </li><li>培养下杆压训练动物用于与下面描述一个试验作为测试会话同一时间调度5-8会话。 </li><li>在日是训练，本左或右杠杆随机，且杆具有控制杆被提出后10秒内被按压，或试用算作无应答的遗漏。由80项试验的为杠杆压训练。 </li><li>一旦动物已经取得遗漏不到10％出80试验中，将其移动到下面侧偏测试。 </li></ol></li><li> 侧面偏置试验 <ol><li>执行一个侧面偏压试验，以确定动物的偏好向左或右控制杆1。试用限嗣继承两旁有两个杠杆压力机。 </li><li>将动物在操作性室，并允许他们选择使用杠杆。在接下来的尝试中，动物有在为了获得奖励以选择相对杠杆。如果动物的第二次尝试是在第一反应的同一侧，给无奖励，继续试验，直至一个响应的相反侧进行。 </li><li>进行一共有7个试验确定动物的一面偏好。 </li></ol></li><li> 测试。 <ol><li>每日会话包含80个试验。 </li><li> 如图1准备一套移程序三个不同的条件。 </li><li>所有的三个条件需要的动物类似行为策略从选择一个杠杆是始终在同一侧（第1阶段，响应策略）与下列一个光提示，指示正确的一面（第2阶段，视觉提示策略）变化。 </li><li>与4届，其中动物有基于杠杆的位置，按一个杠杆的响应策略（一期）的最初的学习开始。在此阶段，正确侧设置到杠杆相反他们的偏好基于如上所述的初步侧偏置测试。 </li><li>接下来，10次动工的视觉线索学习（第2阶段）。无论是杠杆上方照射光提示表明一个正确的控制杆。在这个阶段转变，三迪注意力移位fferent模式可以在三个实验条件下（3.3.6-3.3.8），为描述的进行比较。 </li><li>在设置转移条件1（ 图1A），给在阶段1无光，但光线索表明在第二阶段的正确的一面。在条件1，因此，动物需要参加一种新型的刺激。 </li><li>在集移条件2（ 图1B），提出了一种光球杆正确杠杆上述阶段1，并再次在第2阶段。在这种情况下，光线索已经相关的，但不一定需要在阶段作出选择1。因此动物必须参加到以前相关的线索。 </li><li>在设置转移条件3（ 图1C），随机上述第1阶段因此左或右杆它被忽略开灯提示。在第2阶段的动物需要注意光刺激先前已无关紧要。 </li></ol></li><li> 行为分析。 <ol><li>在整个会议上，测量每天的基础上正确反应，排除遗漏试验的百分比。 </li><li>在先前的研究中1描述计数过程中的视觉线索学习10次累积误差，并将其分为固着，倒退或从未增强的错误。在那里，错误类型的详细分析表明，在设置移动独立的功能。 </li><li>定义持续错误是不正确的反应到先前正确的杠杆，而动物的表现仍然低于机会水平4，6，13，14，15。类似的标准已在以往的研究1，3，7，11被使用。 </li><li>基于一个原则性的方式，确定标准以固着和倒退的错误之间的单独作为该动物先在10个审判的移动窗口得分少于8出10不正确的反应（基于累积二项式分布使得8/10错误或更多= 0.054，概率）点。 </li><li>为了找到这一点，从1开始试ST计算10试用期的移动平均值，然后直到&lt;8/10错误测量了一次试验，一次推进它。开展跨，其中光提示的视觉提示策略在先前不正确杆上方照射的所有试验这种分析。 </li><li>定义所有这一点是倒退的错误后犯下的后续错误。 </li><li>在视觉线索的学习，当动物回应在其上的光线索没有照先前不正确杆算从未增强的错误。将它们分为基于学习阶段的早期或晚期部分;在10届上半年（SESS所犯的错误离子1-5）被认为是早期和那些在下半年（会话6-10）被视为那些晚。 </li></ol></li></ol>

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</ol>

The authors have nothing to disclose.

<html>我们开发对大鼠使用一套既定移范式的新变化。利用这些范式，发现纹状体的胆碱能神经病变损害设定移，提示设置转移纹状体胆碱能的interneurons的一个特定的角色:一个新的规则抑制的旧规则和探索的便利。的影响背内侧和腹侧纹状体之间不同，根据这些结构中学习的不同的作用。 一组移任务已被广泛地用于测试物种从人类啮齿类1，4，5，7，8，9，12的行为的灵活性。术语，"集"是在给定的实验定义为相关行为的刺激财产"外部参照"&gt; 20，21。本研究介绍了这是需要一个主题的基础上发生变化，其中一套是有关改变行为策略的新变化。新的版本应该谨慎使用设置移其他研究进行比较。在一个典型的集换挡模式，主题初步形成相关集来指导行为，并忽略不相关的设定。设定移后，所述受试者具有参加到先前不相干集。在这里我们提出的三个条件，唯一的条件3涉及一组移。条件1和2中，这种组移任务任一个新颖的刺激或化合物刺激的一个子集变得相关不同。学习曲线和完整大鼠持续错误的数量显示在三个条件之间的初始定位及重新定位的差异。因此，每个条件的措施不同的功能:采集到了一种新的线索的响应，注意相关的，但并不重要线索，并注意无关线索。这些新变化是调查了不同形式的行为灵活性的神经机制是有用的。 大鼠有用于研究底层行为灵活性，包括它们的大尺寸使其适用于立体定位手术，转基因菌株的可用性和认知能力的神经机制的许多优点。先前的研究已经建立了基于T-迷宫或大鼠1，7，8，9，11自动设定移任务的版本。在自动操作版本不可用的情况下，在这篇文章中介绍了三种不同的操作都适用于T-迷宫基于集合的转变任务3,7。此外，其他的刺激尺寸不同的感官方式，如气味线索可以组合22，其进一步延伸变化。 以前已经显示的DMS的失活或VS损害设置移时，它需要参加到先前无关刺激7,9。这也是在本研究的条件3的情况。然而，这仍然需要回答一个重要的问题是，是否受损集移由位移或无法关注到在暂时无法改变行动策略（比如从应对策略，以视觉线索策略）派生刺激方案已经在最初的歧视已经无关紧要。这是不可能的，仅通过一个单一的实验内容这两种可能性之间做出选择。若要解除换挡策略更一般的损害的具体注意缺陷，我们已力求创造一套移任务的新变化，使用两个不同耳鼻喉科条件需要相同转变，但是不同类型的关注。 使用这些附加条件，我们可以分开的策略，在不同环境下的转变背后的神经基板。例如，在引入新的刺激条件中的1 VS组大鼠的持续症使我们能够揭示注意过程腹胆碱能系统和方法的潜在机制，以新奇重要的是，新的规则。在另一方面，我们没有观察到病灶DMS上的战略转变一般的效果。相反，这是特定于刺激应变变化和动物需要注意先前不相干线索的情况。两个附加条件成功地控制用于移动策略的一般损害。这使我们得出结论，DMS和VS胆碱能系统在一个旧的战略和探索行为提供便利的抑制的共同作用下，即使他们在工作不同的环境背景下，以及没有一个在换挡策略本身就是一个一般的作用。 总之，一组新移变化使得能够分析大鼠的认知灵活性更详细和帮助下不同环境背景行为灵活性神经机制进一步的了解。未来的研究测试等关键脑区，如前额叶皮层和海马的参与将采用各种情况下这篇文章中介绍了鼓励。

行为的灵活性是在不断变化的世界上生存的关键要求。一个用来测试这种能力既定的行为范式是集移，其中的注意力从一个刺激维度另一个转变是必需的规则改变后改变行动策略。几个脑区域，例如前额叶皮层和纹状体被牵连组移2，3，4，5。此功能的神经机制已经在多个物种（包括人）5，猴子6和大鼠1，7，8，9的影响。然而，集移任务大鼠版本尚未如广泛发展。大鼠的成本效益，其适当的<html>尺寸为立体定向手术，以及最近开发的遗传方式10的可用性，激励为大鼠使用组移范例的进一步发展。 老鼠一组典型的移模式需要两个行为策略之间的变化:例如，应对策略和视觉线索的策略。大鼠最初要选择的两个选项（如在一个操作性自动版本1中的T迷宫版本7，8，9，11左或右杆或左或右臂）之一。一组移位后，他们必须切换到使用视觉提示的策略，如光提示，指示正确的一面。在那些传统的集移的任务，它需要从一个刺激维转移注意力到已经预先不相干另一个方面。 内容】"&gt;除了改变到已经预先不相干的尺寸，也有逻辑可能性刺激以前相关的，或先前不存在，并且现在新的。在自然界中实际生活中的情况下可能需要注意的新的，或从历史相关但不关键线索。因此，我们认为设置移位这些亚型，在啮齿动物的一个新的变化设定换档基于先前建立的自动化组移任务1。 我们最近证明在实验中使用的设定模式发生变化的新版本，以确定纹状体12的神经化学特定病变的效果。在我们以前的研究中，我们有针对性的interneurons胆碱释放背内侧或腹侧纹状体的乙酰胆碱乙酰胆碱以来和这些次区域已经在行为的灵活性受到牵连。所有的实验条件要求相同的战略转移BUt分别参与不同类型的注意力转变:一种新的，以前相关或不相关的先前暗示。我们在这里描述的范式的详细程序，突出代表性的结果表明纹状体胆碱能系统在设定的转移，这是根据行为背景12个不同的纹状体分区域之间的可分离的基础性作用。

<table><tbody><tr><td>Standard Modular Test Chamber</td><td>Med Associates</td><td>ENV-008</td><td></td></tr><tr><td>Low Profile Retractable Response Lever</td><td>Med Associates</td><td>ENV-112CM</td><td></td></tr><tr><td>Stimulus Light for Rat</td><td>Med Associates</td><td>ENV-221M</td><td></td></tr><tr><td>Switchable Dual Pellet/Dipper Receptacle for Rat</td><td>Med Associates</td><td>ENV-202RM-S</td><td></td></tr><tr><td>Head Entry Detector for Rat Receptacles</td><td>Med Associates</td><td>ENV-254-CB</td><td></td></tr><tr><td>Modular Pellet Dispenser; 45 mg for Rat</td><td>Med Associates</td><td>ENV-203M-45</td><td></td></tr><tr><td>Sonalert Module for Rat</td><td>Med Associates</td><td>ENV-223AM</td><td>4.5 kHz available (ENV-223HAM)</td></tr><tr><td>House Light for Rat Chambers</td><td>Med Associates</td><td>ENV-215M</td><td></td></tr><tr><td>SmartCtrl Interface Module, 8 input/16 output</td><td>Med Associates</td><td>DIG-716B</td><td></td></tr><tr><td>SmartCtrl Connection Panel, 8 input/16 output</td><td>Med Associates</td><td>SG-716B</td><td></td></tr><tr><td>45 mg Tablet-Fruit Punch</td><td>TestDiet</td><td>1811255</td><td>Several flavors available</td></tr></tbody></table>

new variations for strategy set-shifting in the rat

行为的灵活性是在不断变化的环境中生存的关键。从广义上讲，行为灵活性要求行为策略的基础上，管限规则变化的转变。我们描述的策略设置移，需要从一个刺激维到另一种注意力转移任务。范式通常用于在灵长类测试认知灵活性。然而，啮齿动物的版本还没有被广泛地作为开发。我们最近通过根据上下文需要注意不同的刺激延伸在大鼠1一套既定移任务。所需的所有实验条件的动物来选择左或右杠杆。最初，所有动物具有到杆的位置的基础上进行选择。随后，在规则的变化发生，这需要在一组从基于位置的规则，其中正确的杠杆是由光线索所指示的规则的移位。我们对THRE性能比较Ë不同版本的任务，其中，所述光刺激要么新颖，先前相关的，或先前不相关的。我们发现，特定的神经化学病灶选择性受损如通过在不同版本的任务的性能测定为使特定类型的组移位的能力。

我们所使用的策略设置移上述调查的interneurons胆碱的行为灵活性的角色任务。我们比较了在背内侧（DMS）的interneurons胆碱的免疫诱导选择性病变的任务的影响，腹侧纹状体（VS）和生理盐水注射的对照。所有动物不得不从选择的基础上侧的杆（左或右），切换到选择的基础上正确的杠杆上方的线索的光。我们使用设置移，其中，球杆光要么的三个实验条件:（1）新的，（2）预先相关（指示正确杆），或（3）预先不相干（随机分配）。 在这三种试验条件下，初始捕获响应策略的是在所有的治疗组完整的，这表明在纹状体胆碱能损失对初始学习（ 图2A - 2C）没有影响。这些结果是一致的与先前的研究示出DMS或VS的失活不影响初始歧视7,9和胆碱能拮抗剂的该应用程序全身16或局部的纹状体17，18，19离开初始学习完好无损。 在集移条件1（ 图2A，新颖的提示），的正确反应百分比为不显著不同。然而，持续错误数比对照组的VS病变组中显著增加。期间设置移条件2（ 图2B，先前相关线索）既不学习性能也不类型的错误是由病变改变。与此相反，在设定变速状态3（ 图2C，先前不相干线索），叔他持续错误的数量群体之间显著不同。特别是，有DMS病变后在持续错误一个显著增加。相比于对照组，从未强化错误的数量在两个DMS和VS病变基团，其在早期，但不是在视觉线索学习的后期明显被显著降低。 总之，VS胆碱能性病变破坏了战略转移时，一个新的刺激被赋予一个新的重要线索，从而导致更多的持续错误。另一方面，DMS病变受影响设置移被要求注意先前无关刺激只有当，造成了不同的分布错误类型。 <img alt="图1" src="/files/ftp_upload/55005/55005fig1.jpg" /> 图1:为一组移三个不同的条件。三流程图该组移范例的变体（A，B和C）。黄色圆圈显示视觉提示。转载来自Aoki 等权限。 12。 <a href="http://ecsource.jove.com/files/ftp_upload/55005/55005fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图2" src="/files/ftp_upload/55005/55005fig2.jpg" /> 图2:在该组移任务行为的结果。在这两个反应和视觉线索策略（左）正确反应比例，显示了每个实验条件类型承诺在视觉线索战略10次（中），和早期决不强化错误（右）晚成分的错误（ A，行为策略的转变需要注意一个新的刺激，B，到以前相关的刺激， <strong&gt; C，到先前无关刺激）。最后一组大小如下:条件1，N = 16（控制），N = 19（DMS），N = 14（VS）;条件2中，n = 13（对照）中，n = 18（DMS）中，n = 14（VS）;条件3中，n = 21（对照）中，n = 17（DMS）中，n = 16（VS）。数据显示为均值±SEM表示。星号*，**和***分别是p &lt;0.05，&lt;0.01和&lt;0.001。转载来自Aoki 等权限。 12。 <a href="http://ecsource.jove.com/files/ftp_upload/55005/55005fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

Watch this Scientific Journal Video about New Variations for Strategy Set-shifting in the Rat at JoVE.com

New Variations for Strategy Set-shifting in the Rat

设置转移，行为灵活性的形式，要求从一维刺激到另一个注意力转移。我们扩展了一个既定的啮齿动物设置移通过根据上下文需要注意对不同刺激的任务1。该任务的具体病变相结合，以确定神经元亚型的顺利转型底层。

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 ...

new-variations-for-strategy-set-shifting-in-the-rat

Nanyang Technological University

Research

JoVE Journal

Behavior

8.2K 次观看.  Okinawa Institute of Science and Technology. 设置转移，行为灵活性的形式，要求从一维刺激到另一个注意力转移。我们扩展了一个既定的啮齿动物设置移通过根据上下文需要注意对不同刺激的任务1。该任务的具体病变相结合，以确定神经元亚型的顺利转型底层。 

视频: New Variations for Strategy Set-shifting in the Rat

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.

The goal of this protocol is to perform a behavioral assay such as the attentional set shifting task (AST) to assess prefrontal cortex-mediated cognitive flexibility in mice.

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 ...

科研

行为学

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 ...

The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their behavioral flexibility and required memory duration, the number of goals and pathways, and also the overall task complexity. A confounding feature in many of these tasks is the lack of control over the strategy employed by the rodents to reach the goal, e.g., allocentric (declarative-like) or egocentric (procedural) based strategies. The double-H maze is a novel water-escape memory task that addresses this issue, by allowing the experimenter to direct the type of strategy learned during the training period. The double-H maze is a transparent device, which consists of a central alleyway with three arms protruding on both sides, along with an escape platform submerged at the extremity of one of these arms.
Rats can be trained using an allocentric strategy by alternating the start position in the maze in an unpredictable manner (see protocol 1; &#167;4.7), thus requiring them to learn the location of the platform based on the available allothetic cues. Alternatively, an egocentric learning strategy (protocol 2; &#167;4.8) can be employed by releasing the rats from the same position during each trial, until they learn the procedural pattern required to reach the goal. This task has been proven to allow for the formation of stable memory traces.
Memory can be probed following the training period in a misleading probe trial, in which the starting position for the rats alternates. Following an egocentric learning paradigm, rats typically resort to an allocentric-based strategy, but only when their initial view on the extra-maze cues differs markedly from their original position. This task is ideally suited to explore the effects of drugs/perturbations on allocentric/egocentric memory performance, as well as the interactions between these two memory systems.

The goal of this protocol is to investigate spatial cognition in rodents. The double-H water maze is a novel test, which is particularly useful to elucidate the different components of learning, consolidation and memory, as well as the interplay of memory systems.

双-H迷宫:一个强大的行为测试学习和记忆的鼠害

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their ...

Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor learning and execution is of critical importance in order to understand the principles and processes that underlie motor function. Here we present a paradigm to study movement acquisition within a daily session of training (within-session) representing the fast learning component and primary acquisition as well as skilled motor learning over several training sessions (between-session) representing the slow learning component and consolidation of the learned task. This behavioral paradigm increases the degree of difficulty and complexity of the motor skill task due to two features: First, the animal realigns its body prior to each pellet retrieval forcing renewed orientation and preventing movement execution from the same angle. Second, pellets are grasped from a vertical post that matches the diameter of the pellet and is placed in front of the cage. This requires a precise grasp for successful pellet retrieval and thus prevents simple pulling of the pellet towards the animal. In combination with novel genetics, imaging and electrophysiological technologies, this behavioral method will aid to understand the morphological, anatomical and molecular underpinnings of motor learning and memory.

A paradigm is presented to analyze the acquisition of a high-precision skilled forelimb reaching task in rats.

收购高精度熟练的前肢到达任务大鼠

Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor ...

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 Structure of Skilled Forelimb Reaching in the Rat: A Movement Rating Scale

Skilled reaching for food is an evolutionary ancient act and is displayed by many animal species, including those in the sister clades of rodents and primates. The video describes a test situation that allows filming of repeated acts of reaching for food by the rat that has been mildly food deprived. A rat is trained to reach through a slot in a holding box for food pellet that it grasps and then places in its mouth for eating. Reaching is accomplished in the main by proximally driven movements of the limb but distal limb movements are used for pronating the paw, grasping the food, and releasing the food into the mouth. Each reach is divided into at least 10 movements of the forelimb and the reaching act is facilitated by postural adjustments. Each of the movements is described and examples of the movements are given from a number of viewing perspectives. By rating each movement element on a 3-point scale, the reach can be quantified. A number of studies have demonstrated that the movement elements are altered by motor system damage, including damage to the motor cortex, basal ganglia, brainstem, and spinal cord. The movements are also altered in neurological conditions that can be modeled in the rat, including Parkinson's disease and Huntington's disease. Thus, the rating scale is useful for quantifying motor impairments and the effectiveness of neural restoration and rehabilitation. Because the reaching act for the rat is very similar to that displayed by humans and nonhuman primates, the scale can be used for comparative purposes. from a number of viewing perspectives. By rating each movement element on a 3-point scale, the reach can be quantified. A number of studies have demonstrated that the movement elements are altered by motor system damage, including damage to the motor cortex, basal ganglia, brainstem, and spinal cord. The movements are also altered in neurological conditions that can be modeled in the rat, including Parkinson's disease and Huntington's disease. Thus, the rating scale is useful for quantifying motor impairments and the effectiveness of neural restoration and rehabilitation.

Experiments on animals were performed in accordance with the guidelines and regulations set forth by the University of Lethbridge Animal Care Committee in accordance with the regulations of the Canadian Council on Animal Care.

The skilled reaching scale divides the movement by a forelimb in a reach for food act into composite elements each of which are evaluated with a three-point scale. The rating scale is described for a normal rat and can be applied toward evaluating neurological motor disorders.

在鼠年达到熟练的前肢结构：一个运动评定量表

Skilled reaching for food is an evolutionary ancient act and is displayed by many animal species, including those in the sister clades of rodents and ...

生物学

Peering into the Dynamics of Social Interactions: Measuring Play Fighting in Rats

Play fighting in the rat involves attack and defense of the nape of the neck, which if contacted, is gently nuzzled with the snout. Because the movements of one animal are countered by the actions of its partner, play fighting is a complex, dynamic interaction. This dynamic complexity raises methodological problems about what to score for experimental studies. We present a scoring schema that is sensitive to the correlated nature of the actions performed. The frequency of play fighting can be measured by counting the number of playful nape attacks occurring per unit time. However, playful defense, as it can only occur in response to attack, is necessarily a contingent measure that is best measured as a percentage (#attacks defended/total # attacks X 100%). How a particular attack is defended against can involve one of several tactics, and these are contingent on defense having taken place; consequently, the type of defense is also best expressed contingently as a percentage. Two experiments illustrate how these measurements can be used to detect the effect of brain damage on play fighting even when there is no effect on overall playfulness. That is, the schema presented here is designed to detect and evaluate changes in the content of play following an experimental treatment.

Play fighting in the rat involves attack and defense of the nape of the neck, which if contacted, is gently nuzzled with the snout. Because the movements of one animal are countered by the actions of its partner, play fighting is a complex, dynamic interaction. This dynamic complexity raises methodological problems about what to score for experimental studies. We present a scoring schema that is sensitive to the correlated nature of the actions performed. Two experiments illustrate how these measurements can be used to detect the effect of brain damage on play fighting even when there is no effect on overall playfulness. That is, the schema presented here is designed to detect and evaluate changes in the content of play following an experimental treatment.

窥视到社会相互作用的动力学测量打打架的影响

Play fighting in the rat involves attack and defense of the nape of the neck, which if contacted, is gently nuzzled with the snout. Because the movements ...

神经科学

A Task for Assessing the Impact of a Partner on the Speed and Accuracy of Motor Performance in Rats

To our knowledge, no study has examined the effect of mere presence on accuracy of performance in animals. Therefore, we developed an experimental task to measure rats&#8217; motor performance (speed and accuracy) in a social condition. Rats were trained to run on a runway and pull down a lever at the end of the runway. In testing, rats performed the task solitarily (single) or in the presence of a confederate rat beyond the lever (pair or a social condition). As indices of the performance speed, we measured the time needed to start running, run through the runway, and pull down the lever. As the index of performance accuracy, we counted the number of trials in which rats could pull down the lever during their first attempt. One-way and two-way repeated-measure analyses of variance were used to analyze the data. This run-and-pull task enabled us to examine the effect of the presence of another conspecific on both speed and accuracy of motor performance in one experiment. The results showed that rats performed the task faster but less accurately in pair sessions than in single sessions. This protocol would be a valid animal model to examine the effect of mere presence on speed and accuracy of motor performance in rats.

A procedure to measure the speed and accuracy of rats&rsquo; motor performance in a social condition is described. The protocol enables us to investigate the effect of the mere presence of others on speed and accuracy of motor performance in one experiment.

评估合作伙伴对大鼠电机性能速度和准确性的影响的任务

To our knowledge, no study has examined the effect of mere presence on accuracy of performance in animals. Therefore, we developed an experimental task to ...

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 ...

A Complex Diving-For-Food Task to Investigate Social Organization and Interactions in Rats

For many species, where status is a vital motivator that can affect health, social hierarchies influence behavior. Social hierarchies that include dominant-submissive relationships are common in both animal and human societies. These relationships can be affected by interactions with others and with their environment, making them difficult to analyze in a controlled study. Rather than a simple dominance hierarchy, this formation has a complicated presentation that allows rats to avoid aggression. Status can be stagnant or mutable, and results in complex societal stratifications. Here we describe a complex diving-for-food task to investigate rodent social hierarchy and behavioral interactions. This animal model may allow us to assess the relationship between a wide range of mental illnesses and social organization, as well as to study the effectiveness of therapy on social dysfunction.

This protocol describes a method of examining social hierarchy in a rat model. Rats perform a complex diving-for-food task in which they form a distinct hierarchy according to their willingness to dive underwater and swim to obtain a food pellet. This method is used to understand decision making and social relationships among highly social animals in small groups.