Name: an operant intra-/extra-dimensional set-shift task for mice
Uploaded: 2016-01-22T14:00:00.000+00:00
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Description: Watch this Scientific Journal Video about An Operant Intra-/Extra-dimensional Set-shift Task for Mice at JoVE.com

We thank G. Pruzzo for his excellent technical assistance and the IIT mechanical workshop for help in building our new apparatus. This research was supported by the Istituto Italiano di Tecnologia, the Marie Curie FP7-Reintegration-Grant N&#176;268247, and by the Italian Ministry of Health Grants for Young Researchers (GR-2010-2315883).

所有程序都经卫生部和当地动物使用委员会意大利教育部并按照指南欧洲共同体理事会指令实验动物的护理和使用进行的。 注意: 图6示出了协议的整个过程，以测试的ID / ED任务的时间线。 1.仪器<img alt="图1" src="/files/ftp_upload/53503/53503fig1.jpg" /> 图1.双室" 操纵子 "装置。（A）中从整个装置的测试过程中模仿鼠标点视图的顶部和（B）的视图从单个腔室的前视图。 1:视觉刺激（发光二极管）; 2:美食杂志; 3:鼻子戳孔; 4:触觉刺激（纹理）; 5:嗅觉的刺激; 6:自动推拉门; 7:房子<html> -光; 8:红外光束的门控。腔室（16×16×16厘米3）由透明塑料门隔开（6）。红外photobeams（8）跟踪的动物的运动和控制的自动门的开/关，以使鼠标来改变腔室。每个室提供了两个鼻戳孔（3）与红外线photobeams，以及在这两者之间，一个食品盒（2）与photobeams其中颗粒状分配器递送的食物加固。房子光（7）位于上述每两个食品杂志。每个鼻戳孔装配有一系列多变的刺激，可能会发生变化在三种不同的知觉尺寸（气味，视图，圆通）的。最初发表于"最终的区域内和异次元注意定平移任务的小鼠"19。 <a href="https://www.jove.com/files/ftp_upload/53503/53503fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 内容"&gt;注意: 操纵子装置（图1）由两个相同的腔室与树脂玻璃墙和铝地板（16×16×16厘米3的每个腔室）庭通过透明有机玻璃除以门，可以是自动分离。控制，让鼠标进入任一室，每室有两个鼻子戳孔，红外photobeams，而且，他们两人之间，photobeams其中颗粒机提供的食品强化食品杂志，一个风扇和一所房子，光设上述每两个食品杂志。 <ol><li>装备有一个数字可变刺激（ 表1），该变化在三种不同尺寸的感知（即，气味，视觉，触觉）的每个鼻戳孔。注意: 在表1中提出的刺激，以避免任何混淆因素和/或偏压由于避免或偏好已被选中。五对榜样的每个维度的允许使用在学科测试的所有班次，用在每个班次新刺激。 <ol><li>为了提供嗅觉刺激到鼻子戳孔，通过自动干燥剂，过滤，补水和控制对气味的演示文稿中使用稀释嗅觉，这种条件下进气的鼻子戳孔。 <ol><li>使用一个嗅觉来控制两个鼻子戳孔。通过空气泵和真空去除鼻子戳孔香味调节气流。空气泵连接到嗅觉计的入口和真空到安装在鼻子戳设备上的插座。然后连接插座的气味传递至每个鼻子戳入口。调节流速，以每分钟1.5升。 </li><li>稀释气味气味的矿物油1:20，填补了嗅觉的瓶子。 </li></ol></li><li>对于视觉刺激 ，代替发光二极管（LED），每个鼻戳孔的顶部将其固定在金属P腔室的头面板（参见图 1和表 1的细节）。它们连接到输出接口。 </li><li>对于触觉刺激 ，多变的安装地板的纹理在每个鼻子戳洞前。安装在滑动支承的不同质地和移动使用框架的地板的下面，以使它们在每个鼻戳孔的前面的地板上的小开口（3×3厘米2）的对应关系呈现。 </li></ol></li><li>控制根据制造商的，以便在实验过程中，自动改变不同尺寸的刺激指示使用软件的刺激的呈现。 </li><li>放置在该装置的顶部上的相机，以便使用行为监测软件记录基底交替和运动活动（例如，Ethovision，Anymaze），这可能有助于消除有问题无关的认知功能的动物。 </li></ol><table fo:保持-together.within页="1"&gt; <tbody><tr height="21"><td height="21" style="height:21px;width:152px;"> 气味 </td><td style="width:284px;"> TEXTURES </td><td style="width:159px;"> 灯 </td></tr><tr height="23"><td height="23" style="height:23px;">桃诉圣人</td><td>魔术贴诉电影</td><td>灯诉灯关闭</td></tr><tr height="21"><td height="21" style="height:21px;">香草诉熏衣草</td><td>粗砂纸打磨诉细砂纸</td><td>红诉绿</td></tr><tr height="21"><td height="21" style="height:21px;">草莓诉肉桂</td><td>光滑的纸板诉脊纸板</td><td>蓝诉黄</td></tr><tr height="21"><td height="21" style="height:21px;">柚子诉牛</td><td>海绵诉光滑的塑料</td><td>橙色诉白</td></tr><tr height="21"><td height="21" style="height:21px;">柠檬诉杏</td><td> honeycOMB纸诉铝箔</td><td>修复灯诉闪烁的灯光</td></tr></tbody></table> 表1.模范在ID / ED 操纵子任务中使用。化合物歧视是基于对范例的固定组合（参见图2为歧视的序列的一个例子）。从不同维度的榜样对列于随意组合。中性刺激的不同维度分别是:空气流量，没有香味;白皮书;没有光的刺激。表最初发表于"终极区域内和异次元注意定平移任务的小鼠"19。 2.动物的制备 注:这里所报告的代表性结果从雄性C57BL / 6J小鼠获得的，3至7个月大，在光相位。 <ol><li>称取鼠，单独的内部，然后处理1分钟三隔日。 </li><li>驯化单外壳，记录体重和24小时摄食量的一周后，连续三天，以确定基线体重和食物摄取。 </li><li>为测试训练前应用略有食物匮乏方案1周。检查动物的体重，每天的食物，同时限制整个实验过程中，以保持约90％的基线自由喂养体重。对于习惯训练阶段之前连续三天，给老鼠在他们的家笼也≈20食物强化颗粒。这些是将要在随后的测试中使用的食物颗粒。 注意:食物限制用于增加动物的动机在任务的工作，但是，在整个过程中的任何阶段不超过重量损失的10％，因为它可能导致不正常行为和过大的应力为小鼠，这可能影响结果。 <ol><li>可替代地，为了避免单个外壳，乐AVE小鼠群养（2至4每个笼子），并让使用者自由采食食物的时间测试后，一个特定时期。检查动物的体重，每天的食物，同时限制整个实验过程中，以保持约90％的基线自由喂养体重。 </li></ol></li></ol> 3，习惯化<ol><li>培养小鼠在40分钟的1天的会议，移动设备内没有门分隔，其中鼻子戳在任何鼻子戳孔导致在食品容器中的颗粒输送。在这个阶段，只能使用中性刺激（表1）对所有不同尺寸（习惯化1）。 </li><li>在接下来的一天，训练动物40分钟，以从一个腔室移动到另一种在每个试验（习惯化2）的末端。对于所有不同尺寸只能使用中性刺激。此外，在此阶段，一个鼻戳在任何的鼻子戳孔导致在食品盒的颗粒递送。当鼠标检索在食品杂志奖励，降低分压门，得到鼠标进入另一个室为下一次试验。 </li><li>第三天（习惯化3），训练动物执行两个简单的歧视（SD1和SD2; 例如，魔术贴VS薄膜;在VS光提示灯提示关闭;桃花VS圣人）至8正确反应的标准连续出了10次试验。不要在测试的下一个阶段的再次使用这些范例。 <ol><li>启动，将鼠标在一个腔室与中性刺激，而在另一个腔室中的刺激线索被接通;然后降低门，得到鼠标访问与活化的刺激提示该室。鼠标要学会选择其中正确的刺激呈现的鼻子戳洞。会话持续40分钟。 </li><li>奖励鼻子戳在正确的洞小球传递，当鼠标进入食品杂志社，降低分门得到鼠标进入另一个室为下一次试验。不要奖励鼻子戳不正确的洞，打开房子的光，持续5秒。然后降低门，得到鼠标进入另一个室为下一次试验。 </li><li>进行各段的前十个试验作为成形试验:如果鼠标选择了不正确的孔，记录一个错误，但不终止试验直到鼠标还戳在正确的孔。在随后的试验中，如果鼠标捅不正确的洞，记录一个错误，并关闭所有维刺激终止审理。 </li><li> 40分钟后终止每个会话或鼠标无法使连续五分钟，取其首先出现任何回应。如果鼠标不能在一个会话达到标准，继续第二天的测试。 </li><li>如果经过5次鼠标无法达到习惯化3的SD1或SD2的标准，停止测试鼠标和研究消除它，因为它是不是能够可靠地执行可能会影响以后的ID / ED任务的结果基本歧视。 </li></ol></li></ol><img alt="图2" src="/files/ftp_upload/53503/53503fig2.jpg" /> 图的ID / ED的任务2为例，该ID的一个例子/ ED"卡住，在设置"和"二维"范例所示。从"最终的区域内和异次元注意定平移任务的小鼠"19改编。 <a href="https://www.jove.com/files/ftp_upload/53503/53503fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 4."固定型的设置"ID / ED范例程序注意:在此过程中，先前在两个灵长类和啮齿类7,15,16使用，有必要操纵三个不同的知觉尺寸每个单独的鼠标测试。至于习惯相，所有的测试日常会话开始放置鼠标在两个腔室，其中所有的刺激是中性之一。试验开始前，刺激线索在相反的腔接通。然后分割门被降低，得到鼠标进入另一个室，其中的刺激是线索上。 <ol><li>要训练动物发展出一套，或偏见，对特定的感性维度（如，气味，光线或地板纹理），小鼠暴露在这个顺序提出以下歧视（参见图2为例）: <ol><li>为简单识别（SD）引入小鼠的维度（气味，光或纹理， 见图 2）是相关于直到EDS的所有任务。也就是说，相关尺寸是一个指示，其中正确的响应是。以下图2的例子中，本2的气味，如弗吉尼亚州nilla（01）和薰衣草（O2），并选择01作为正确的响应。 </li><li>对于复合歧视（CD），引入第二个层面，例如光，这是无关紧要的（ 即没有说明是正确的响应）。本两个灯（L1和L2），并结合气味（O1和O2），以便有两个可能的歧视（参见实施例中的图2）。正确的和不正确的范例中的相同中的SD。 </li><li>对于复合歧视（CDRE）的逆转，离开了范例和相关尺寸不变，但有动物得知以前正确的刺激，现在不正确。例如，选择薰衣草作为正确的响应，香草是现在不正确的选择。这些相同的条件下，会发现对于其他反转阶段（ 即 IDSRe，IDS2Re和EDSRe）。 </li><li>之后，选择一个内部维移（IDS），其中新的范例既用于相关和无关的尺寸（一个总的变化设计）。例如，使用草莓和肉桂（O3和O4）的气味和蓝色和黄色的灯光（L3和L4）作为灯。然而，确保测试科目保持以便找到正确的反应相同的相关尺寸如下。这些相同的条件下会被发现为其他intradimensional转变（ 即 IDS2）。 </li><li>至于以前的歧视，有老鼠进行内部维移（IDSRe）的逆转。使用相同的条件CDRE。 </li><li>对于内维变速2（IDS2），使用相同的条件IDS中。 </li><li>类似地，使用相同的条件CDRE为内维移逆转2（IDSRe2）。 </li><li>在额外维移（EDS），已在老鼠选择一个新的刺激呈现后的尺寸正确的孔。从一个新的方面，这是纹理呈现的一对刺激。例如使用粗砂纸打磨（T1）为正确的资源ponse和细砂纸（T2）是不正确的，并用两个新的气味呈现出来，例如柠檬和杏（O7和O8）。现在，先前相关方面已变得无关紧要。不要出现以前不相关的尺寸了。 </li><li>对于额外的维反转（EDSRe），使用相同的条件CDRE。 </li></ol></li><li>测量小鼠的表现，直到他们达到8正确选择的标准出10个连续的试验中，以完成每个阶段。设置程序（见表材料），以在达到标准后自动移动到下一个阶段。停止日常会话40分钟后，或者如果鼠标无法正常进行，连续5分钟均回应，终止会话，并继续第二天用鼠标在它离开的地方同台演出。 <ol><li>对于每个阶段，测量达到标准的时间。如果鼠标无法在一个会话达到标准，总结在连续几届会议所作的总时间。对于每次试验，测量从演示的刺激（气味，灯光，纹理）的时间到鼻子戳反应（延迟响应）。 </li></ol></li><li>在每届会议结束时，擦拭用70％酒精的设备。 </li><li>使用总是歧视的顺序相同。然而，随意改变的刺激尺寸和使用范例的对，同样的实验组中代表他们和他们抗衡组之间。 </li><li>确保平等地平衡内部和各实验组之间使用的感性维度，这样每个可能的ED移位表示（即，光气味，光线的质感，气味淡，气味纹理，质地轻，质地异味） 。榜样的组合更是不胜枚举能够全面平衡;因此，为了减少自由度，始终使用范本中对;例如，香草刺激用薰衣草等（见表1）。 </li></ol>注:另一个条件来衡量注意力集中移能力，同时使用灵长类动物12,17和13的啮齿动物，是"两维"模式。在这种情况下，只有两个感性尺寸用于在整个测试。 <ol><li>对于这个协议，使用歧视的顺序，并按照所描述为&#39;卡住，在设置"协议到EDS阶段的过程（参见图2为例）: <ol><li>用于SD和以下阶段，使用相同的对的"卡住合集&#39;的，直到IDS2Re。 如图2的例子中，使用两个气味（O1和O2，使用01作为正确的刺激）。 </li><li>对于CD，如&#39;卡住合集&#39;协议，引入一个新的尺寸（例如光，L1和L2），这是无关紧要的，将作为一个混杂因素。 </li><li>该CDRE类似于我n中的"固定型的集"的协议，从而留下了典范和相关尺寸不变，但有动物得知以前正确的刺激，现在不正确（ 如 01）。 </li><li>在IDS中，使用总是对新的刺激的两个维度（O3和O4，L3和L4，其中O3是正确的刺激）的。 </li><li>对于IDSRe，有老鼠执行IDS的逆转。选择正确的榜样是这样的，这就是一个在IDS（ 例如，O4）不正确。 </li><li>对于IDS2，推出新的刺激对两种尺寸（O5和O6，L5和L6）的。 </li><li>如前面的反转阶段，在IDS2Re，有动物得知先前正确刺激为现在不正确（例如，O5）。 </li><li>对于"两维"协议中，EDS，老鼠要选择正确的响应后，以前不相关的尺寸现在变成了相关的尺寸。因此，光是新的相关尺寸，WHICH指示正确的反应。特别是，红光（L7）是正确的响应。相反，先前的相关尺寸（在这个例子中，气味）现在是无关紧要的。 </li><li>在EDS，为反转（EDSRe）后，用同样的条件CDRE。相关尺寸是一样的，在EDS但正确的和不正确的范例被反转。因此，例如，绿色光（L8）现在是正确的响应。 </li></ol></li></ol> 6.数据分析<ol><li>衡量性能:试验次数达到标准;时间达到标准（以分钟计）;从表现刺激到鼻子戳响应时间（延迟响应）。 </li><li>进行统计分析，使用方差分析与不同阶段（SD，光碟，CDRE，IDS，IDSRe，IDS2，IDSRe2，EDS，和EDSR​​e），为受试者内因素来检查达到标准规定的试验次数，定时所需完成每个阶段和延迟响应。刀豆管道事后分析使用纽曼- Keuls检验。注:显着性的接受值P &lt;0.05。 </li></ol>

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The authors declare that they have no financial conflicts of interest.

在这项研究中，我们提出了一种新的自动两腔ID / ED"操纵子"的任务，老鼠即能可靠地测量通过逆转学习，注意力集中的形成和转移认知灵活性。这种模式是类似的WCST和ID / ED任务，在人类和灵长类常用克服了以前版本的啮齿动物的主要限制。此操纵子的范例可以作为一个新的有效的工具，大药物和/或在小鼠中具有高的相关性，以转化医学相关的认知（发育不良）功能的遗传筛查。 这种自动化的任务已经比以前使用的ID / ED任务啮齿类动物具有以下优点:（1）它具有比手动版本，劳动密集程度较低的程序（例如，软件调节任务的各个阶段，极大地减少干预的。实验者）; （2）它消除主观性在测量parame任何来源TER值（例如，实验者不需要判断动物是否已经实际进行的选择响应）; （3）它消除老鼠可能需要遵循加强相关线索，以便做出响应的任何可能性（ 即报酬总是自动在该中心的杂志提供）; （4）避免了任意的环境条件（例如，使用迷宫和不同尺寸/材料，设备，使用手工制作提示刺激）; （5），它允许操作三个不同尺寸的具有大范围的不同的刺激，按照在临床环境中使用的等效人工任务。在这里，我们目前只有来自小鼠的数据，但类似的优点可能也将老鼠。 有在任务关键步骤，这是可用于以鉴定areliable注意力定移性能内部构建-有效性参数:在EDS COMPARⅰ）表现较差ED之前的阶段II）的IDS一般改善IDS2;三）在连续的反转阶段一个具体的改善，为更多的动物是在设定逆转培训，更好的后续之内设定的退步20应执行;在EDSRe四）更好的性能相比，EDS。这种新颖的ID / ED操纵子任务提供所有这些功能，在使用该CANTAB ID / ED任务灵长类和在使用手册"挖"12,13版本啮齿类与先前研究一致。此外，该自动化任务的每个阶段学了同等的实验中，不论使用 （即，气味，质地轻）19相关/不相关的维度。这表明，所有使用的刺激物有类似的显着性和适合于注意力集-形成和/或移位。我们的实验表明，在解决EDS的难度也强调了增加的响应延迟。处理时间增大到时更难歧视21保持最佳精度。因此，考虑延迟来响应作为信息处理，决策和解决问题18的速度的索引，EDS的期间较慢潜伏期可能反映通过面对在解决集变速困难的策略。 我们已经表明，我们的新颖装置可以被有效地与更多的"经典的"注意力定移范例仅采用两个维度在整个测试（即，两维）使用或与一个固定型中设定的范例，这意味着使用三个维度。根据感兴趣的认知领域，可以选择最合适的协议。这两个范例已在人类，灵长类动物和啮齿类动物7,12-17以前使用过。但是， 固定型中设定的程序是能够设定变速的不同组件之间进行区分，并且点矿石额叶功能的选择性措施在人类患者7,22。此外，可能发生在两维模式的一个问题是所学习无关强权偏压的结果。据悉无关perseveration指的是不能参加和了解，这在以前无关7的信息。这种情况可能发生在两维模式的EDS相位，作为主题需要的注意力转移到先前不相干尺寸。在这种情况下，基本上是不可能辨别的EDS赤字是否是由于无法从一个先前的相关尺寸和/或无法现在注意力转移到一个先前不相干维上转移开注意力。减值然后只是反映了回应先前作出无关通过其与强化的反馈随机关联维度的有效抑制。与此相反，在固定型中设置 CONDITION，故障转移到新的相关尺寸不能归因于这个层面，因为它以前没有经历过任何事先学习。失败，因此，反映perseveration到以前相关的维度。总之，即使在正常的野生型小鼠中的"固定型中设置"和"两维"注意力定移范例可能产生类似的结果，我们明确地更喜欢卡住合设置perseveration为原因所讨论以上。

注意定势移是认知灵活性和执行功能1的措施。它指的是任意的内部规则（"认知注意力集"）之间切换的能力。用于测量注意力定换挡和认知灵活性在人类中使用最广泛的神经心理任务是威斯康星卡片分类测试（WCST）2和一个较新的，更精版本:所述内和额外尺寸注意力定移（ID / ED）剑桥神经心理学测试自动化电池（CANTAB）3,4。这些任务已经被用于识别在广泛的精神障碍包括自闭症5，精神分裂症6，帕金森氏病7，强迫症8和注意力缺陷/多动障碍9的特定认知异常。临床相关性和WCST和ID的固体方式方法/ ED测试都ATT在类似的测试实施临床前研究10,11 racted兴趣。这些任务允许不同的认知能力，如歧视性的学习，逆转学习，形成一个注意力集中的在同一主题中的选择性测量，注意在同一维度中移动（ 即 ，内维转变:IDS）之间和不同感性维度（ 即额外维的转变:EDS）。这是至关重要的，因为不同的脑回路，以及神经病理学可能改变以不同的方式，这些不同的认知功能。例如，一个双重分离或功能专门化的效果已经证明的横向（在猴子和人）/内侧（在啮齿动物）和在PFC中的注意力定移任务轨道区域之间。当眶额皮层是更多地参与这些任务的反转阶段，横向/内侧PFC区管辖额外维度转变阶段12-14。 这些注意力集中移测试灵长类动物的啮齿动物版本已经成功生成13-16。然而，这些啮齿动物版本的一些方面已经限制了它们的应用和使用。例如，这些任务手动运行，因此，劳动密集型和难以标准化。此外，食品增强剂的存在下，刺激内部可能导致动物的反应和潜在偏差在选择决策10暧昧解释。这些特性限制测试的吞吐量和，更重要的是，它们在大规模的遗传和/或药物筛选研究应用。 为了克服这些限制，并以提高的ID / ED移范例在啮齿类动物中的潜在应用，我们在这里提出了一种新的双室操作性基于任务的小鼠进行测试认知灵活性。这种新颖的任务密切模仿人类和非使用的ID / ED任务人类的灵长类动物和规避早期版本的啮齿动物的问题。

<table><tbody><tr><td>Plexiglas walls and aluminum floor</td><td>Custom made</td><td></td><td>(16 x 16 x 16 cm for each chamber)</td></tr><tr><td>Plexiglas door&amp;nbsp;</td><td>Custom made</td><td></td><td></td></tr><tr><td>PC</td><td>Dell Inc.</td><td></td><td></td></tr><tr><td>MED-PC IV software&amp;nbsp;</td><td>(Med Associates, St. Albans, VT, USA)</td><td>custom made</td><td>Use an operant code in order to automatically control the presentation of the stimuli and the sequence of the stages</td></tr><tr><td>Nose-poke hole&amp;nbsp;</td><td>Med Associates, St. Albans, VT, USA)</td><td>ENV-314M</td><td></td></tr><tr><td>Food magazine&amp;nbsp;</td><td>Med Associates, St. Albans, VT, USA)</td><td>ENV-303M</td><td></td></tr><tr><td>Pellet dispenser for food reinforcement&amp;nbsp;</td><td>Med Associates, St. Albans, VT, USA)</td><td>ENV-203-14P</td><td></td></tr><tr><td>Houselight&amp;nbsp;</td><td>Med Associates, St. Albans, VT, USA)</td><td>ENV-315M</td><td></td></tr><tr><td>Dilution olfactometer&amp;nbsp;</td><td>(Med Associates, St. Albans, VT, USA)</td><td>PHM-275</td><td></td></tr><tr><td>Liquid odorants</td><td>(Sigma Aldrich, Dorset, UK)</td><td></td><td>(see Table 1)</td></tr><tr><td>Mineral oil</td><td>(Sigma Aldrich, Dorset, UK)</td><td>M5904</td><td></td></tr><tr><td>Air pump and vacuum</td><td>(Med Associates, St. Albans, VT, USA)</td><td>PHM-280</td><td>Vacuum is recommended for scents removal at the end of each trial</td></tr><tr><td>Light-emitting diodes (LED)</td><td></td><td></td><td>High-intensity, transparent gem, 3 mm</td></tr><tr><td>Floor textures</td><td></td><td></td><td>3x3 cm</td></tr><tr><td>Reinforcement pellets</td><td>TestDiet</td><td>5TUL 14mg</td><td>For mice</td></tr></tbody></table>

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.

图2示出的ID / ED任务的一个例子。刺激（无论是"歧视1"或"歧视2&#39;）对，被随机赠送的各个阶段，以及鼠标必须选择正确的激励每一对。在本实施例表，正确的范例被报告为粗体。在第一阶段（SD或简单歧视），在两个鼻戳孔呈现的刺激不同在三个维度中的一个（例如，O1:香草与O 2:薰衣草） 并且鼠标奖励选择正确的榜样（ 如 01）。一旦受试者达到标准在这个阶段，在下一阶段（CD或化合物歧视）开始时，如有关维度的相同范例由第二的范例呈现叠加在随机的，但不相关的维度，导入作为混杂因素（ 例如 ，L1:蓝光vs.L2:黄灯亮）。两个不同的歧视是可能在该阶段（eitheR&#39;歧视1&#39;或&#39;歧视2&#39;）。在下一阶段（CDRE或化合物歧视反转），奖励意外事件被颠倒，但范例和相关尺寸不变:鼠标具有得知先前正确刺激为现在不正确（例如，薰衣草气味现已奖励）。在下一阶段（IDS或帧内维移），新的范例（既气味和灯）被引入，但（在该例子气味）有关的尺寸保持不变（例如，草莓是正确的选择）。在下一阶段（IDR或帧内维反转），奖励意外事件是相反的。一个第二帧内维移位（IDS2和它的反转）之后，新的范例被引入到测试额外尺寸移（EDS），其中的有关尺寸被改变。在"卡功能于集"EDS，鼠标把重点放在了新的维度（如纹理，T1:粗砂纸打磨与 T2:精SAndpaper），而先前的相关尺寸（在此情况下，臭味）现在是无关紧要的尺寸。在"二维"的EDS，先前不相干尺寸（在此情况下，光）现在是有关的尺寸。在最后阶段（EDSRe或额外尺寸反转），奖励意外事件是相反的。 为了获得可靠的结果，在任务中使用的刺激物的尺寸应同样教训。 如图3，视觉，触觉和气味歧视在这种新颖的装置所需类似时间（F（2,64）= 0.36; P = 0.69）和类似的实验中（F（2,64）= 0.059; P = 0.94）要达到的标准，这表明动物能够进行简单的歧视，无论提出的维度。 如果一个可靠注意力定已经发展了任务，p的测试阶段一个正常的野生型小鼠的erformance应较差EDS中阶段相比之前和之后的阶段中所报告的在啮齿类和灵长类12,13先前的研究。尤其是，时间和达到所需标准试验一个强劲增长应在EDS中找到比较到IDS阶段。 如图4所示，在我们的实验中与&#39;卡住合设置&#39;协议，小鼠的性能分析显示的识别效果进行试验的数据（F（8,168）= 9.23; P &lt;0.0001）和时间（ F（8,168）= 8.62，P &lt;0.0001），以达到标准要求。事实上，需要更多的老鼠试验和更多的时间来解决EDS阶段相比，CD，IDS，IDS2和EDSRe阶段（P &lt;0.05; 图4A-B）。同样，性能与"两维"协议（图5）进行测试分析表明为试验次数一个显著歧视效应（F（8.72）= 30.66; P &lt;0.005）和时间（F（8.72）= 4.65，P &lt;0.0005），需要达到的标准。的确，我们表明，需要更多的小鼠试验（P &lt;0.05）和更多的时间（P &lt;0.05），解决了EDS相比光碟，IDS IDS2和EDSRe（图5A-B）。在转移的能力没有差异应该具有不同尺寸的测试小鼠之间观察到。 在一个正常的野生型小鼠中，第一反转学习（ 即 ，CDRE）比初始判别（即，光盘）更困难。在协议，如从图 4和5可知，小鼠需要更多的试验（P &lt;0.05;图4-5A）和更多的时间（P &lt;0.05;图4-5B）来完成这个阶段。此外，反转的表现应该从提高CDRE到IDSRe到IDS2Re，为大家展示我们的实验都"陷入集"和"二维"的协议。这些resulTS进一步加强通过任务形成一个注意力集中的证据。 在整个任务中，将小鼠提高它们的速度来响应在连续阶段。因此，延迟响应的分析表明一个显著歧视效应（F（8,200）= 42.59; P &lt;0.0001）。特别是，这表现在图4C代表性的结果的等待时间戳在IDS2阶段下降相比，在IDS中，光盘和SD级（P &lt;0.0005）。此外，延迟，反应在EDS阶段相比以前的IDS2和IDS2Re和连续EDSRe阶段（P &lt;0.05）增加。与这些结果行，等待时间的分析"两维"工作期间作出回应也表现出歧视显著的影响（F（7,63）= 9.98，P &lt;0.0005）。 如图5C所示，延迟作出选择瓦特EDS的期间相比前IDS2和IDS2Re和连续EDSRe（P &lt;0.05），为增加。由于延迟响应已经被认为决策处理18的一个索引，这些结果进一步表明，小鼠遇到了一些问题处理EDS期间新判别规则。基于野生型小鼠（图4-5）的行为表现，我们确定样本大小（由R功率分析）对于每个实验组的最小数量应为8。 <img alt="图3" src="/files/ftp_upload/53503/53503fig3.jpg" /> 光，气味和质地图3.简单的歧视是等价的。试验（A）号和要达到的标准简单的歧视，只有光线，气味或纹理的刺激要求（B）的时间。数值代表平均值±SEM整个图2-4。数据ORIginally发表在"终极区域内和异次元注意定平移任务的小鼠"19。 <img alt="图4" src="/files/ftp_upload/53503/53503fig4.jpg" /> 在"卡，在设定的"ID / ED 操纵子 任务。（A）试验，（B）时间图4.野生型C57BL6J雄性小鼠的表现 （以分钟计），并达到标准中的不同阶段所需的天该ID / ED 操纵子任务，采用"卡，在设定的"ID / ED范例。 （℃）时间 （秒），则分隔门的开口，并且在任务的不同阶段鼻戳响应（延迟响应）之间经过。共有26只小鼠进行了测试; 4只小鼠被排除，因为他们没有可靠戳的培训中获取食物强化或未能完成电子ntire过程。答:* P &lt;0.05与CD，IDS，IDS2，IDS2Re和EDSR​​e; B:* P &lt;0.05相对于光盘，IDS2，IDS2Re和EDSR​​e。 A和B:＃P &lt;0.05，## P &lt;0.005与CD，IDSRe和IDS2Re。 C:* P &lt;0.05与IDS2，IDS2Re和EDSR​​e。注意，小鼠能够完成整个任务中5-9天中报道在图3-4全部实验。数据最初发表于"最终的区域内和异次元注意定平移任务的小鼠"19。 <a href="https://www.jove.com/files/ftp_upload/53503/53503fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图5" src="/files/ftp_upload/53503/53503fig5.jpg" /> 图 5，在"两维"野生型C57BL6J雄性小鼠表现ID / ED操纵子任务。（A）试验，（B）的时间（分钟）和到达标准中使用两维模式的ID / ED 操纵子任务的不同阶段所需的天。 （℃）时间 （秒），则分隔门的开口，并且在任务的不同阶段鼻戳响应（延迟响应）之间经过。共有13只小鼠进行了测试; 3只小鼠被排除，因为他们没有可靠戳的培训中获取食物强化或未能完成整个程序。 A和B:＃P &lt;0.05与CD和IDS2Re，* P &lt;0.05与CD，IDS，IDS2，EDSRe。 C:* P &lt;0.05与IDS2，IDS2Re和EDSR​​e。数据最初发表于"最终的区域内和异次元注意定平移任务的小鼠"19。 <a href="https://www.jove.com/files/ftp_upload/53503/53503fig5large.jpg" target="_blank">请点击此处</a>查看该图的放大版本。 <img alt="图6" src="/files/ftp_upload/53503/53503fig6.jpg" /> 图6.时间轴协议的整个过程来测试ID / ED的任务。 <table fo:keep-together.within-page="1"><tbody><tr><td> 阶段 </td><td> 描述 </td><td> 补充笔记 </td><td> 参考 </td></tr><tr><td> 简单的歧视（SD） </td><td></td><td></td><td></td></tr><tr><td> 复合歧视（CD） </td><td>刺激改变两个感性尺寸，例如颜色和形状的视觉刺激的人工任务，或之间的质地和气味刺激的啮齿动物</td><td></td><td></td></tr><tr><td> 逆转学习（CDRE - IDSRe - IDS2Re - EDSRe） </td><td>两个典范一个感性的层面在S中有他们的强化突发逆转，这样什么以前正确的是那么不正确，反之亦然） </td><td>在串行逆转学习，绩效与连续在设定逆转改善。因此，反转阶段（ 即 ，CDRE，IDSRe，IDS2Re）不仅是评估不同的皮层区域的功能，也有利于1）形成认知-注意力集中在EDS阶段的挑战，和2），以防止迷信调理意外刺激的方面</td><td> - 小鼠眶额皮质的病变（Bissonette等人，2008），并monkyes受损冲销学习（Dias的等，1996。） - 功能磁共振成像过程中的逆转学习的性能表现（和汉普郡欧文，2006）激活眶额皮层的</td></tr><tr><td> Intradimensional移（IDS - IDS2） </td><td>新颖范例进行介绍，但相同的尺寸被加强</td><td> IDS阶段小号ERVE作为关键内部控制（即，EDS应该比IDS更加困难），并且也有助于形成认知注意力集</td><td>在PFC多巴胺耗竭受损注意力集中形成（Robbins和罗伯茨，2007年）。 6-OHDA受损猴没有表现出经典减少从第一（IDS1）中的错误的减少到最后（IDS5）歧视，这应该反映获取的注意力集</td></tr><tr><td rowspan="2"> 异次元移（EDS） </td><td> "坚持，在设置"协议:以前无关刺激维度取而代之的是一个新的刺激维度这立即成为有关</td><td>故障转移到新的相关尺寸不能归因于这个层面，因为它以前没有经历过任何事先学习。失败，因此，反映perseveration先前有关维</td><td> - 在HAV内侧前额叶皮质的病变Ë已经显示损害EDS在小鼠（Bissonette等人，2008年），和mokeys（迪亚斯等，1996） - 额叶病人受损的卡，在设定的"perseveration"条件，但不是在"两维"的条件（Owen等，1993） - 小鼠多巴胺在mPFC的调制的EDS性能（帕帕莱奥等人，2008; Scheggia等人，2014）和大鼠（滕布里奇韦等人，2004。） </td></tr><tr><td> "两个方面"协议:以前不相关的维度增强</td><td>可能会出现一个明显的故障转移注意力集中在一个主体能够从之前相关方面上转移注意力（当它变得无关紧要），但是，尽管如此，无法重新关注新的相关维度上</td><td> - 在mPFC的大鼠（比勒尔和Brown，2000）的受损病变EDS移 - 在腹外侧PFC（新罕布什尔州和欧文，2006年）期间对EDS的性能功能磁共振成像已被证明激活60; </td></tr></tbody></table> 表2:的ID / EDØ 庇隆 任务说明任务的阶段，包括引用病变及药理研究解决涉及任务的过程中测试了不同的结构脑区的作用阶段 。

Watch this Scientific Journal Video about An Operant Intra-/Extra-dimensional Set-shift Task for Mice at JoVE.com

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

一个操作性内/外维特班任务的小鼠

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.

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

an-operant-intra-extra-dimensional-set-shift-task-for-mice

Research

JoVE Journal

Behavior

12.1K 次观看.  Istituto Italiano di Tecnologia. 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.

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

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 ...

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

A Behavioral Assay for Investigating the Role of Spatial Memory During Instinctive Defense in Mice

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often stereotyped actions elicited in response to innately aversive sensory stimuli, but their success requires enough flexibility for adapting to different spatial environments, which can change rapidly. Here, we describe a behavioral assay to evaluate the influence of learned spatial knowledge on defensive behaviors in mice. We have adapted the widely used Barnes maze spatial memory assay to investigate how mice navigate to a shelter during escape responses to innately aversive sensory stimuli in a novel environment, and how they adapt to acute changes in the environment. This new assay is an ethological paradigm that does not require training and exploits the natural exploration patterns and navigation strategies in mice. We propose that the set of protocols described here are a powerful means of studying goal-directed behaviors and stimulus-triggered navigation, which should be of interest to both the fields of instinctive behaviors and spatial memory.

This protocol describes a behavioral assay, based on the Barnes maze test, to study how instinctive defensive actions are modified by the knowledge of spatial environment.

一种研究空间记忆在小鼠本能防御中作用的行为分析法

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often ...

Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget

Ethologically relevant behavioral testing is a critical component of any study that uses mouse models to study the cognitive effects of various physiological or pathological changes. The object location task (OLT) and the novel object recognition task (NORT) are two effective behavioral tasks commonly used to reveal the function and relative health of specific brain regions involved in memory. While both of these tests exploit the inherent preference of mice for the novelty to reveal memory for previously encountered objects, the OLT primarily evaluates spatial learning, which relies heavily on hippocampal activity. The NORT, in contrast, evaluates non-spatial learning of object identity, which relies on multiple brain regions. Both tasks require an open-field-testing arena, objects with equivalent intrinsic value to mice, appropriate environmental cues, and video recording equipment and the software. Commercially available systems, while convenient, can be costly. This manuscript details a simple, cost-effective method for building the arenas and setting up the equipment necessary to perform the OLT and NORT. Furthermore, the manuscript describes an efficient testing protocol that incorporates both OLT and NORT and provides typical methods for data acquisition and analysis, as well as representative results. Successful completion of these tests can provide valuable insight into the memory function of various mouse model systems and appraise the underlying neural regions that support these functions.

Here we provide a protocol which includes comprehensive instructions for the economical establishment of murine object location and novel object recognition behavioral testing, including the design, cost, and construction of required equipment as well as execution of behavioral testing, data collection, and analysis.

一种新的小鼠目标识别与目标定位行为测试

Ethologically relevant behavioral testing is a critical component of any study that uses mouse models to study the cognitive effects of various ...

Two Different Real-Time Place Preference Paradigms Using Optogenetics within the Ventral Tegmental Area of the Mouse

Understanding how neuronal activation leads to specific behavioral output is fundamental for modern neuroscience. Combining optogenetics in rodents with behavioral testing in validated paradigms allows the measurement of behavioral consequences upon stimulation of distinct neurons in real-time with high spatial and temporal selectivity, and thus the establishment of causal relationships between neuronal activation and behavior. Here, we describe a step-by-step protocol for a real-time place preference (RT-PP) paradigm, a modified version of the classical conditioned place preference (CPP) test. The RT-PP is performed in a three-compartment apparatus and can be utilized to answer if optogenetic stimulation of a specific neuronal population is rewarding or aversive. We also describe an alternative version of the RT-PP protocol, the so-called neutral compartment preference (NCP) protocol, which can be used to confirm aversion. The two approaches are based on extensions of classical methodology originating from behavioral pharmacology and recent implementation of optogenetics within the neuroscience field. Apart from measuring place preference in real time, these setups can also give information regarding conditioned behavior. We provide easy-to-follow step-by-step protocols alongside examples of our own data and discuss important aspects to consider when applying these types of experiments.

Here we present two easy-to-follow step-by-step protocols for place preference paradigms using optogenetics in mice. Using these two different setups, preference and avoidance behaviors can be solidly assessed within the same apparatus with high spatial and temporal selectivity, and in a straightforward manner.

在小鼠的文室内使用光遗传学的两种不同的实时位置偏好范式

Understanding how neuronal activation leads to specific behavioral output is fundamental for modern neuroscience. Combining optogenetics in rodents with ...

Optogenetic Manipulation of Neuronal Activity to Modulate Behavior in Freely Moving Mice

Optogenetic modulation of neuronal circuits in freely moving mice affects acute and long-term behavior. This method is able to perform manipulations of single neurons and region-specific transmitter release, up to whole neuronal circuitries in the central nervous system, and allows the direct measurement of behavioral outcomes. Neurons express optogenetic tools via an injection of viral vectors carrying the DNA of choice, such as Channelrhodopsin2 (ChR2). Light is brought into specific brain regions via chronic optical implants that terminate directly above the target region. After two weeks of recovery and proper tool-expression, mice can be repeatedly used for behavioral tests with optogenetic stimulation of the neurons of interest.
Optogenetic modulation has a high temporal and spatial resolution that can be accomplished with high cell specificity, compared to the commonly used methods such as chemical or electrical stimulation. The light does not harm neuronal tissue and can therefore be used for long-term experiments as well as for multiple behavioral experiments in one mouse. The possibilities of optogenetic tools are nearly unlimited and enable the activation or silencing of whole neurons, or even the manipulation of a specific receptor type by light.
The results of such behavioral experiments with integrated optogenetic stimulation directly visualizes changes in behavior caused by the manipulation. The behavior of the same animal without light stimulation as a baseline is a good control for induced changes. This allows a detailed overview of neuronal types or neurotransmitter systems involved in specific behaviors, such as anxiety. The plasticity of neuronal networks can also be investigated in great detail through long-term stimulation or behavioral observations after optical stimulation. Optogenetics will help to enlighten neuronal signaling in several kinds of neurological diseases.

With optogenetic manipulation of specific neuronal populations or brain regions, behavior can be modified with high temporal and spatial resolution in freely moving animals. By using different optogenetic tools in combination with chronically implanted optical fibers, a variety of neuronal modulations and behavioral testing can be performed.

神经活性的光遗传学操作，调节自由移动小鼠的行为

Optogenetic modulation of neuronal circuits in freely moving mice affects acute and long-term behavior. This method is able to perform manipulations of ...

A Behavioral Task Modeling 'Everyday Memory' in an Event Arena to Foster Allocentric Representations for Rodents

The event arena provides an optimal platform to investigate learning and memory. The appetitive everyday memory task described in this paper provides a robust protocol for the investigation of episodic and spatial memory in rodents, which specifically fosters allocentric memory representation. Rats are trained to find and dig for food during the encoding phase and, after a time delay, rats are given a choice to find the reward food pellet in the correct location. There are two key elements that promote the use of an allocentric strategy in this protocol: 1) rats start from different start locations within and between sessions, 2) a stable home-base is deployed where rats have to carry their food to eat. By means of these modifications, we effectively encourage the rodents to use allocentric spatial representations to perform the task. In addition, the task provides a good paradigm for within-subject experimental design and allows experimenters to manipulate different conditions to reduce variability. Used in conjunction with behavioral and physiological techniques, the resulting rodent model provides an effective test-bed for future research into memory formation and retention.

The goal of this optimized 'everyday memory' protocol in an event arena was to employ a stable home-base that encourages the use of allocentric spatial representations. This animal model provides an effective test-bed for future research into the formation and retention of event memories using behavioral and physiological techniques.

The event arena provides an optimal platform to investigate learning and memory. The appetitive everyday memory task described in this paper provides a ...