Research described here was supported by a grant from the Natural Sciences and Engineering Research Council of Canada to S.B.F.

注:此处描述的被批准的机构动物护理和使用委员会（IACUC）在马里兰州圣玛丽学院，或加拿大议会动物保健在不​​列颠哥伦比亚大学的所有程序。 1.动物<ol><li>使用成年雄性SD或成年雄性Long-Evans大鼠。 注:虽然跨越这两个品系在性能上的差异并没有经过正式测试，Long-Evans大鼠倾向于获取视觉线索的歧视（见下文），比SD大鼠（Floresco，未发表意见）稍快。 </li><li>抵达后，在集落，房子成年大鼠单独或组，这取决于实验的需要和设施的限制。使用单住房的实验中，动物是食物限制，为客户提供更好的控制食物摄入量。让动物适应环境的殖民地（不处理或食物的限制）的后至少3天到来。 注:最近的一份报告建议，实验者性别可能产生不利影响的痛苦和焦虑的行为24，结果措施，可以延伸到其他应力敏感的行为，包括认知。在我们的研究中，我们并没有观察到老鼠训练的男性与女性处理任何明显的性能差异，虽然我们没有正式评估这一点。 </li><li>开始行为测试之前每天处理动物为每个约3-5分钟，至少3天。上的处理的第一天，获得一种自由馈送重量每只大鼠。目标重量为食物限制，如果使用的话，将是本自由重量的85-90％。请注意，此目标重量， 例如 ，在实验室笔记本或动物的笼子卡上。在某些情况下，可以不需要食物限制，如果所使用的加强件是非常可口（ 如甜奶），虽然动物可能变得与使用这种加强件的饱足太快。 </li><li>在EAC小时处理的天，因为每个动物的处理完成后，放置约10-20奖励粒料动物的家笼驯化大鼠（谁通常neophobic），以将在任务中使用的补强内（见第2.1.3节下文）。 </li><li>在搬运三天，逐步减少动物的日常食物摄入量，以使他们自己的目标权重。务必注明上笼卡或其他文件，这些动物现在对限制饮食。 注:尤其是食品的限制要求IACUC机构或其他监管机构之前的任何程序，就可以开始批准。一般的程序如下批准由作者各自的体制机构;一定要咨询任何适当的地方和/或国家指导方针，在个别机构的其他要求。 </li><li>每周称量动物至少两次监测健康和确保动物没有大幅下降BELOW目标重量。保证水是免费提供在任何时候。 </li></ol> 2.设备和软件<ol><li>使用配有（至少）操作室2伸缩杆，两个激励灯，一houselight，和一个加强分配器对于这些任务。 <ol><li>将杠杆在中央加强交付面积两侧有一个刺激位于每一杆上面。 </li><li>确保houselight照射而不会与检测的刺激灯， 例如干扰整个室中，放置houselight墙壁上的杠杆和刺激灯对面。 </li><li>加固用可口的食物（ 如蔗糖颗粒20,21或蔗糖溶液25）。无论它是表示要"加强动物"下面，将一份45毫克蔗糖颗粒或蔗糖溶液1规定的量。 </li></ol></li><li>控制刺激呈现，杠杆操作，实际上，并通过与计算机的接口的数据收集。与作者联系，了解有关写入MED-PC软件，专门针对行为测试和数据采集设计了一个计划任务程序的具体信息。 注意:用于行为测试的程序的一个重要特征是，以试验-通过试行关键变量，包括球杆的光的位置上，由动物所选择的控制杆的记录，该动物是否作出了正确的，不正确或无反应（遗漏）和延迟作出选择。这些数据是用于特定类型的过程中的选择顺序的不同部分制成的错误的评估关键的，这将在下面说明。 </li><li>在训练前开始，分配给每个动物的操作性室在那里将每一天整个实验进行测试。试验动物每天的整个实验在大约相同的时间。 </li><li>定期清洁操作室（至少每周一次）与SOAp和水和/或抗微生物溶液。 </li></ol> 3.训练前注:一旦动物已经达到了他们的目标食物重量的限制，他们可能会开始塑造的操作性商会。训练前的程序通常需要约10-20天，老鼠之间的实质性变化。参见图1C为程序的概述。 <ol><li>形动物杠杆记者。 <ol><li>下一个固定比率（FR）-1加固的时间表， 即列车动物，一个加强被递送给每个控制杆按。整形可以施用或者与两个杆延伸（一按上要么是钢筋），或在一个杠杆在一个时间（ 例如 ，每天一杆）的顺序（左/右）跨越动物和/或实验条件平衡。 <ol><li>对于延长两个杆成形，继续整形会话（1 30分钟的会话每天）直到动物适应至少5的最小标准每节0-60印刷机连续两天。这通常需要大约3-6天。 </li><li>用于整形各杆独立，继续在第一杠杆会话，直到动物上呈现的第一杆响应至少50-60倍。随后的整形会话应该使用相反的杆，直到老鼠再次达到这一标准。通常情况下，这第二个标准是迅速取得老鼠已经学会后，按第一杆。 注意:每次塑造一个杠杆将需要更长的时间（动物必须符合标准两次，一次为每个杠杆），但将确保动物得到两个杠杆之间的经验响应，并交替，任务的重要组成部分描述如下。 </li></ol></li></ol></li><li>给动物伸缩杆训练会话来与杆的延伸和回缩他们熟悉，并确保将大鼠使得相对少的遗漏（通常&lt;5）的时候，他们继续到任务主要测试阶段。 <ol><li>每次试验，决定延长其杠杆。以伪随机顺序交替杆扩展，有45左杆试验和45右杆试验，但没有连续超过两次试验延长同杆。 </li><li>扩展选定杠杆。加强动物要按下此杆在10秒内，在此之后，控制杆缩回。 </li><li>如果动物不能在10秒内作出反应，收回杆和录制遗漏。 </li><li>开始试验，每20秒在整个会议期间。 注:在伸缩杆训练，预曝光来刺激光（无论是左和右灯的刺激后，每个杠杆延长照明） 可以用来减少的面板灯的新颖性和显着性，并且因此增加了后续的难度设置移任务20。使用此过程将显着增加，以实现标准射孔所需试验次数rmance上的视觉提示的歧视如下所述，和动物可能需要数天来学习这些条件下，这条规则。 </li><li>继续伸缩杆的培训课程（每天一次30分钟的会议）的固定天数，或者直到动物符合五个或更少遗漏的最低标准，连续两个交易日。这通常需要约5-10天。 <ol><li>对于使用尖锐的操作（ 如药物测试）的研究，使用天固定数量（ 如 5天），以确保所有的老鼠收到类似接触到的杠杆。 </li></ol></li></ol></li><li>评估动物侧偏好。 <ol><li>行为方偏好伸缩杆训练上届会议后立即测试（在同一天，参见图1C）。侧优先任务包括七个试验中，其中的每一个2和8次试验由一个固定的20秒intertrial间隔（ITI）分隔间组成。 </li><li>上每个子试验中，两杆延伸进入腔室，持续10秒或直到杠杆按下作出响应。在这一阶段的训练不亮的灯光刺激。 </li><li>加强对各审判的第一子试验要么杆的响应，并记录为"最初的反应。" <ol><li>不加强对在同一个试验中后续子试验相同的杠杆响应。允许最多一个试验在相同的杠杆六个随后的反应，之后给予强制子的审判。强行子试验仅由相对杆被扩展为10秒或直至反应制成的。 </li></ol></li><li>下面就每次试验的初步反应，加强在对面杆的第一反应，然后终止试验。因此，每个试验（含有多达八个子试验）内，将动物在每个杠杆响应至少一次要求的。 </li><li>定义每个动物的一侧优先的一侧在其上majorit初始反应Ÿ发生（至少有四个七个试验）。 </li><li>然而，如果动物不成比例响应在整个会话1杆（定义为大于2:1的比例），记录该侧作为动物的偏好。 </li><li>开始侧偏好测试后，测试在一个连续的一天。 注:在我们的经验，大多数动物没有显示偏强的偏好。对于那些做的，要求他们按在响应辨别训练他们的偏见相反的杠杆确保他们正在学习与杠杆相关的，而不是仅仅响应上首选杠杆的具体回应回报不时之需。 </li></ol></li></ol> 4.测试注:动物可在三个序列，其每一个包括两个不同的任务中的一个进行测试。战略转移是使用评估（1）设置平移从线索响应和/或（2）设置平移的响应提示; řeversal学习使用响应（3）逆转评估。 （第四个可能的序列，提示逆转，不建议在下面讨论的原因。） <ol><li>关于任务和序列的一般信息。 <ol><li>进行连续数天每个序列。每个序列需要至少两天（初分辨学习，然后转移或反转）。 </li><li>在一个单一的任务中使用的最大为150至200次试验的，这取决于实验的性质。 （请注意，使用的试验更高的数字将总会话时间一定会增加至60分钟或更大，它可以是一个要考虑的因素，使用化合物与动作的持续时间更短的药理试验。） </li><li>对于每一个序列，在一个任务（"设置"）试验动物后跟一个第二任务（"移位"或"逆转"）。试验动物为最多上的每个任务3天（ 即 ，450-600试验），最多6天总。 <ol><li>拆除动物没有在3天内达到标准从实验的第一个任务（"设置"）。 </li><li>动物不中的第二个任务（"移"或"逆转"）3天到达标准，分配要得高分的试验，以标准表示经历过试验的数量（ 即 450试验的150试验3天每个）。 </li><li>如果任务参数已经被修改，以便控制动物可以实现单日表现的标准，然后修改任务，使所有大鼠只给出了一个测试环节，并给予那些不审判的分配数内达到标准最高得分（150-200试验，具体取决于任务已配置）。 </li><li>在转移或逆转的任务，有动物要么启动一个会话不必立即执行新规则，或给他们20"提醒"试验，他们执行的任务利用在训练的第一阶段学到的规则，然后在规则会话期间，22开关。 注意:此后一种方法是对实验评估潜在的促 - 认知化合物可改善柔韧性的，因为它可以用来阐明的换档/逆转时更好的性能是否是由于专门增强的灵活性或受损的先前规则检索特别有用的是可以在换档过程中促进一个新的学习。 </li></ol></li></ol></li><li>设置移:提示任务，以响应任务。 <ol><li>开始对提示任务（ 见图1A），这加强动物为下面的照射刺激光（跳转）的控制杆响应测试动物。提示任务是在这个序列中的"设置"任务。 <ol><li>开始每次试验与缩回两种杠杆。 </li><li>照亮左或右的刺激光为3秒;然后两杆延伸到室10秒，直到响应发生。 </li><li>加强对信号杆只有一个正确的回应。当在任杆的响应，收回杠杆。 </li><li>开始试验，每20秒在整个会议期间。伪随机地确定，使得不连续两个以上的试验发生具有相同的刺激光（左或右）照射试验的顺序。 </li><li>继续试验，直到动物达到的标准（连续完成10正确的反应），并已完成至少30次试验，或直到150-200试验是在没有达到标准完成。 </li><li>如果未在第一天达到标准，再次测试第二天上提示任务的动物，但取出的要求完成至少30次试验。如果未在第二天达到标准，测试按照相同的程序在第三天动物。 </li></ol></li><li>第二天就提示任务达到标准后，动物转移到</strong&gt;的响应任务（ 见图1B），它强化了无论刺激光（CUE）照明动物就在自己身边的偏好相反的杠杆响应。响应任务是在这个序列中的"移位"的任务。 <ol><li>开始每次试验与缩回两种杠杆。 </li><li>照亮左或右的刺激光为3秒;然后两杆延伸到室10秒或直至反应发生。 （请注意，刺激光的位置是无关紧要的用于此任务。） </li><li>加强仅在正确的位置上杆的响应（左或右，动物的侧偏好对面）。当在任杆的响应，收回杠杆。 </li><li>开始试验，每20秒在整个会议期间。伪随机地确定，使得不连续两个以上的试验发生具有相同的刺激光（左或右）照射试验的顺序。 </li><li>继续试验，直到动物已达到标准（完成10个连续正确反应），或直至150试验是在没有达到标准完成。 </li><li>如果未在第一天达到标准，再次测试的响应的任务的动物上的第二日。如果未在第二天达到标准，测试按照相同的程序在第三天动物。 </li></ol></li></ol></li></ol><img alt="图1" src="/files/ftp_upload/52387/52387fig1highres.jpg" /> 图1:歧视任务用于设置平移顺序此图显示在提示到响应顺序执行的任务;注意，该任务是相同的，只是在相反的顺序，在响应对提示序列:（A）在视觉线索辨别学习，动物被加强对下照射激励光杠杆的应答。（B）的在反应歧视的学习，一个imals被加强用于对一个杠杆响应（左或右），而不管刺激的光的位置的。（C）的 流程图描绘了一个典型的战略转移的实验，从训练前测试序列的训练阶段。 <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/52387/52387fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="3"><li>设置移:响应克尤。 注意:此序列是一个有利于大多数来自加法的视觉线索光预曝光条件以训练前20,21（参见上述步骤3.2.4）。以往的研究表明在伸缩杆培训预曝光老鼠灯作出反应到提示换挡更加困难，依赖于内侧前额叶皮质。相反，前额叶inactivations不损害这种类型的转变，如果这些训练前程序不雇用20。 <ol> &lt;LI&gt;开始动物的反应任务，加强动物就在自己身边的偏好相反的杠杆响应测试，无论刺激光（CUE）照明。响应任务是在这个序列中的"设置"任务。 <ol><li>与测试继续详见步骤4.2.2（响应任务）以上。 </li><li>有动物完成这个任务至少30次试验，因为它是"设置"任务。 </li></ol></li><li>上的响应的任务到达标准后的第二天，移动物于提示任务，这加强了动物上下方照射刺激光（跳转）的控制杆响应。提示任务是在这个序列中的"移位"的任务。 <ol><li>与测试继续详见4.2.1步（提示的任务）以上。当该任务是"移"的任务并不需要的30次试验完成的最低要求。 </li></ol></li></ol></li><li>逆转响应。 <ol><li>开始动物测试的响应任务，加强不管刺激光（CUE）照明动物就在自己身边的偏好相反的杠杆响应。响应任务是在这个序列中的"设置"任务。 <ol><li>进行上述测试步骤4.2.2（响应任务）的详细。 </li><li>有动物完成这个任务至少30次试验，因为它是"设置"任务。 </li></ol></li><li>上的响应的任务到达标准后的第二天，对一个反转响应的任务，这加强动物在相对 ​​杆响应作为对所述第一任务的试验动物， 即 ，杆对应于它们的原边的偏好。这个新的响应的任务是在该序列的"反转"的任务。 <ol><li>与测试进行如下详述将在上面步骤4.2.2，所不同的是钢筋杆位置现在等于动物的原方偏好。 </li></ol></li></ol></li></ol> 5.行为的措施<ol><li>记录试验，以规范双方的"设置"任务和"转移"的任务。试验，以标准的主要测量精度的，被定义为完成10个连续的试验中，包括那些10次试验所需的试验次数。需要注意的是遗漏的数量应被考虑这项措施出来（ 例如 ，如果老鼠需要100试验达到标准，使10遗漏，实际试验，标准是90）。 </li><li>算上之前的标准做出错误的数量达到双方的"设置"任务和"转移"的任务。误差准则是准确性，可以更灵敏比试验，以规范和不受增加遗漏率的一种辅助措施。 </li><li>对于转变错误类型，进一步分析错误做出一套移序列的"移位"的任务类型。 <ol><li>指望一个错误，"固着/倒退式"当动物根据，这是正确的前一天的"设置"任务中的规则不正确地响应对"转变"的任务。然后，使用下列准则分别划分这种类型的错误，到固着和倒退。 <ol><li>划分"转移"到会的16个连续完成的试验（不包括省略试验）块。内的每个块中，确定哪些错误适合这种类型的， 即定义，大鼠取得对应于该"设置"任务规则的不正确的响应。将有最大的这种类型中的16项试验的每个块的8个可能的错误。 </li><li>分数确定错误的固着，直到少于六人在块内进行。 </li><li>通过任务的端部开始与下一个块并继续进行，得分这种类型是倒退的错误。 </li><li>如果动物是在为"Sh测试IFT"上超过一天的工作，继续得分错误，犹如该块是连续的。 </li></ol></li><li>计数错误"永不增强"当动物响应不正确的"Shift"键的任务与响应，这不是在任的"设置"或"Shift"键的任务是正确的。 </li></ol></li><li>逆转的错误类型，进一步分析错误就逆转学习序列的"逆转"的任务类型。 （1）进入固着和倒退的错误，以及（2）到朝向-牵引和外之牵引错误:反转错误沿着两个维度进行细分。 <ol><li>共划分成错误和固着倒退。 <ol><li>划分"逆转"会变成16个连续完成试验块。算误差在每个块（最多16个错误是可能的）。 </li><li>分数误差为固着，直到少于10人的块内进行。&lt;/ li&gt; <li>通过任务的结束与开始的下一个块和继续，比分错误的倒退。 </li><li>如果动物是在"逆转"任务上超过一天进行测试，继续得分错误，犹如该块是连续的。 </li></ol></li><li>共划分成错误朝-分心（刺激光不正确的，按下手柄上面照）和外之分心（刺激光是正确的，未按杠杆上方照射）。 </li></ol></li><li>记录省略试验次数，以提供动物的动机水平的广泛的措施。 <ol><li>检查每天的测试环节后，遗漏的分数，以排除设备故障，可以通过高遗漏分数来表示。 </li><li>在缺乏设备故障，排除动物遗漏数据异常高的数字在任的任务遗漏（一般≥3高于平均标准偏差）的。 </li></ol></li><li>记录响应延迟，通过测量时间控制杆延伸和响应之间经过的时间。延迟提供一个粗略的测度运动功能和/或处理的速度。 </li></ol>

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E., 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=Olfactory+exposure+to+males,+including+men,+causes+stress+and+related+analgesia+in+rodents.">Olfactory exposure to males, including men, causes stress and related analgesia in rodents.</a> Nature methods. 11, 629-632 (2014).</li><li>Trantham-Davidson, H., 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=Chronic+alcohol+disrupts+dopamine+receptor+activity+and+the+cognitive+function+of+the+medial+prefrontal+cortex.">Chronic alcohol disrupts dopamine receptor activity and the cognitive function of the medial prefrontal cortex.</a> J Neurosci. 34, 3706-3718 (2014).</li><li>Ghods-Sharifi, S., Haluk, D. M., Floresco, S. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+effects+of+inactivation+of+the+orbitofrontal+cortex+on+strategy+set-shifting+and+reversal+learning.">Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning.</a> Neurobiol Learn Mem. 89, 567-573 (2008).</li><li>Boulougouris, V., Dalley, J. W., Robbins, T. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+orbitofrontal,+infralimbic+and+prelimbic+cortical+lesions+on+serial+spatial+reversal+learning+in+the+rat.">Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial reversal learning in the rat.</a> Behav Brain Res. 179, 219-228 (2007).</li><li>Tseng, K. Y., Chambers, R. A., Lipska, B. 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出版并免费使用这个手稿是由医学Associates，Inc.的支持

行为的开发任务在啮齿类动物来衡量高阶认知结构是必不可少的推进认知神经生物学的知识。随着构建良好的和验证任务，老鼠可以在复杂的相媲美的灵长类动物，甚至人类的工作进行评估。在这里，我们已经展示了如何执行功能，战略转移和逆转学习两个方面，可以在啮齿类动物中使用自动化技术操作性研究。使用这些自动化的任务，我们已经复制有关组移动和反转学习11,13,18-21,27,29的神经基质以前的研究结果在交叉迷宫和挖掘工作，这表明操作性任务是这些有效的评估构建。 这些自动化的任务有许多优于现有的非自动交叉迷宫和挖掘工作的好处和优点。最引人注目的是数据采集的自动化操作性版的卓越率。每一天的培训或测试只需要30-60分钟，并且是全电脑控制的要求实验者最小的监督。此外，一些动物可以同时使用的多室操作性安装测试。每个任务系列，从成型到最终的测试，可以在大约2-3周内完成。的自动化的任务的另一个重要的优点是刺激呈现的精确控制，从而减少实验者错误的可能性。例如，呈现在每个试验提示位置的顺序是随机的和控制的计算机，而不是由一个实验者手动咨询一个试通过审列表。试验之间的定时精确测量和一致的，而不是由它采用实验者， 例如 ，从交叉迷宫除去大鼠或重新排列挖掘容器时混淆。加固交付是自动的，并不受实验者错误（ 例如 ，忘记了饵交叉迷宫的正确手臂）。数据的收集同样改善，响应模式，包括精确的响应延迟测量自动录像。在没有其他运动异常，改变的响应延迟可以用来推断改变处理速度的证据和/或判断的认知任务21,22的复杂程度。 的自动化的任务还保留的横迷宫任务之一重要的优点:要进行错误就移位或反转日类型的详细分析的能力。是复制前一天的策略（固着或倒退的错误）表示以前未尝试过的策略（从未增强误差）集移误差和错误之间的区别可以协助在行为上的灵活性特征的特定缺陷。特别是，在测试初期出现的持续错误反映动物的无法抛弃以前的STrategy，而后来发生的回归错误反映动物的无法维持的新战略一旦perseveration已停止20。从来没有增强的错误可能表明不能获得新的战略，或无法根据规则20系统作出回应。以前的研究结果表明16,17,20这些类型的错误的可分离神经解剖学基础，也解释了这些任务的成果有价值。 我们的程序已经开发和老鼠进行了优化。这是说，其他团体也使用了类似的程序测试设置转移能力的小鼠31。然而，某些修改需要用小鼠以适应物种差异被采用。这些包括较长的介绍之前杠杆延伸，训练过使用30次试验/天，不正确的选择之后超时惩罚掺入多天的视觉提示的光。 AlthouGH这些修饰使该测定少与药理挑战的使用，它可以证明，以评估在遗传改造的小鼠认知灵活性（尽管还不清楚这些修饰是否会保持该任务的额叶皮层灵敏度）有用顺从。 当然，也有限制这些任务。其中的一些局限性产生于任务的自动化性质，而其他的都与任务本身的参数。关于后者，在这里所描述的集移任务（以及交叉迷宫设置移任务26）利用一组受限制的刺激和响应。不像挖任务，在其上的新范例（ 例如 ，不熟悉的香味或挖介质）可用于在每个阶段11,19来构造新的注意力集，操作性集移任务必然需要两个刺激是熟悉的之间进行选择动物 - 无论是左与正确的提示灯，或左与右的位置。这意味着操作性和交叉迷宫组移任务涉及响应冲突以及策略换档，虽然一个人的策略转移到一个新的，以前无关刺激维度概念被保留20,23。与此相关，集移和逆转此处所述不允许第三个刺激维度，如挖掘任务可能包括挖媒体，气味，纹理11,19操作性任务。但是，我们并不认为这是一个致命的缺陷，作为操作性设置转移的任务仍然需要动物打压先前有关歧视的战略，并出席了以前被忽视的刺激维度。此外，似乎可以想象的修改，设备和任务参数可以支持附加的第三刺激尺寸，诸如听觉提示或气味，尽管这些增加可能会使学习更加困难和更小火焰nable到单日药理试验。 最后，任何操作性为基础的任务，一个潜在的限制是对大鼠行为的直接信息的丢失- 即实验者不再看着老鼠。我们认为通过自动化赋予客观性和数据收集速度的优势足以弥补这方面的损失，并安装在操作室相机是一种比较简单的方法，如果希望恢复单个可视门禁。 有若干可采取使用这些操作性任务最大化成功步骤。首先，处理训练开始都不为过前动物的重要性;如同任何行为的任务，精心处理的动物更容易使用，少强调，并往往会产生更少的可变数据。其次，有些试点可能需要确定一天进行测试的最佳时机;我们光周期内测试，并发现performanCE是最佳的，当动物接近这个周期结束测试（ 例如 ，大约下午4时00分的光循环下午7:00结束）。第三，应注意，以确认性能建立在每个训练前阶段稳定之前的动物前进到下一个步骤。例如，一致的和强大的性能的伸缩杆训练阶段是在"设置"歧视任务精通性能优良的预测。至于装备，尽管所有的步骤都是自动的，实验者的干预仍然是必要的，以确认所有部件是否正常。例如，一个设备检查应每天运行（或多于一天一次，如果大量的动物正在测试），以确保所有的灯，杠杆，和奖励递送系统是可操作的。特别是，在奖励输送系统（特别是粒料分配器）的故障可以大大影响性能。非常多的疏漏之处对某一天可能表明一个问题与奖励输送设备，从而数据输出应当由实验者熟悉任务和预期的性能水平，每天进行检查。在不存在设备故障的，具有高数遗漏的可能表示其他问题动机或动物的健康。如果动物是健康的，否则，食物限制可以增加取动物自由摄食重量的80-85％，很短的时间，直到性能恢复。 这些设置移和反转任务可以在各种实验范式中使用。例如，操作的效果，如病变，发育护理，饮食操作，长期药物治疗，或遗传修饰可以进行调查。而在该组变速或反转阶段的处理的效果可能是主要感兴趣的，请注意，因为这样的慢性或长期的治疗，必须一定TRAI之前施用宁开始，对性能多个阶段的影响（特别是在初始歧视或"集"），还必须检查21。使用急性处理，如药物治疗或临时神经解剖学inactivati​​ons的，是特别适用于这些任务。在这样的情况下，增加了一个第三组（ 如图2）是很有用的;因此，初级实验组接收的上移或反转的天感兴趣的操纵，而一个控制组上接收初始歧视或"设置"来测试对学习广泛影响的天操纵，以及第二控制组接受无操作（或假治疗）这两天20,22。注意，对于这样的急性操纵研究，最好是与该组初始的学习期间，匹配大鼠的性能和它们分配到实验组和（第二）对照组相应。这种微量在用于表征可能是在性能上治疗引起的差异可能由个体变异老鼠怎么容易学会的刺激区分羞愧。此外，如果一个实验需要多个队列的数周或数月的测试中，每个队列应包括来自所有实验组的动物。例如，一个研究的换档期间测试的急性药理操纵的影响，可能需要48只大鼠中总的和3个实验组，在每16动物3组进行试验。在这种情况下，每个队列应包含5-6大鼠在每个实验组。理想情况下，统计分析应包括确认全国共有大鼠每个队列在性能上没有差异的一个因素。最后，这些操作性任务可以是施加在体内的记录技术，包括微透析，伏安法，和电，由于组件是特别有用的，例如在受控环境中，刺激presentat的精确定时离子和响应，并且不是在交叉迷宫或挖任务可用或实际动物的受限制的运动。

高层次的认知过程，包括规则产生，行为选择和策略评估被统称为"执行功能"或"行为灵活性1"。这样的方法是至关重要的正常的认知功能，并且可在这些不同的疾病如精神分裂症被削弱，酗酒，抑郁症，中风和阿尔茨海默氏病2-7。执行功能过程的调控主要通过的区域在额叶皮质介导，包括背外侧前额叶皮层和在人类8-10眶额皮质。 任务的发展，评估执行功能和/或在非人类的动物，特别是啮齿动物行为的灵活性，极大地推进认知11-14的神经生物学的理解。这样的任务使人们有可能分别测量的行为灵活性不同的组件，包括战略转移和逆转学习。战略转移是指能够有效抑制先前学习的应对策略，而获得了新的，竞争的策略，特别是在整个刺激尺寸（异次元移动） - 例如 ，从执行视觉歧视（红色与绿色，红色的是开关"正确"和触觉刺激无关）来进行触觉辨别（平滑与粗糙的，光滑的地方是"正确"的视觉刺激，现在无关）。在另一方面，逆转学习还涉及应对策略的改变，但同样的刺激维度内- 例如 ，在"红与绿"举例来说，如果红色是以前正确的，逆转将决定绿色现在是正确的，而触觉刺激仍将无关。 几个任务已经开发了以调查在啮齿类动物的行为的灵活性。 交叉马泽任务需要的动物首先学习无论是基于方向的规则（ 如 "总是向右转"）或视觉为基础的规则（ 如 "始终把对视觉提示"），以一定的性能标准。然后，将动物需要意外移位或者跨越模式到相对规则（ 策略换档 ，原本被称为"nonreversal转移"15），或在模态转变为相反的应变（ 反转学习 ）13,14,16。这类任务是在皮层和皮层下的网络中断敏感，涉及前额叶皮层，丘脑和纹状体1,13,14,16-18。另一种类型的注意力集移任务（有时称为挖任务 ），需要训练动物两个容器沿两个或三个刺激尺寸（挖媒体，气味，和/或外部纹理）不同来区分。类似于交叉迷宫任务，动物则需要转移或者跨维度（战略转移）或同一维度内（逆转学习），而这些任务都同样敏感的额叶皮质操作11,19。这个任务的一个优点是，额外的维策略转移期间，大鼠都带有新颖多组刺激（范例）的，这确保了在此阶段性能损害可能归因于能力的中断转移注意力集到不同的方面化合物的刺激，而不是一个能力受损停止接近先前与奖励相关联的特定的刺激。但是，此功能也使得它更难以在一组换挡确定赤字的具体性质。 虽然上述的任务已经很好记载在文献中，它们都从多个程序的缺点的苦，时间主要长度需要给试验动物。在这两种交叉迷宫任务和挖掘任务中，只有一个动物可以在同一时间进行测试;此外，测试必须施用实时由专用实验者，并可能需要多达每每只动物每天几个小时。此外，刺激的呈现和在两种类型的任务的行为反应的记录由实验者手动控制的，并因此易受人为错误的主观解释。 在这里，我们描述了用于评估策略移位和反转学习在大鼠，使用简化的刺激控制和数据演示，并大大提高了数据采集的速率和吞吐量20,21操作性程序的自动化方法。用来塑造和列车大鼠中描述的方法，以及任务本身和所得到的数据进行分析的部件。我们已发现，像交叉迷宫和挖掘任务，这些自动化任务是在额叶前中断敏感和皮层下的电路，以及对一个神经发育操纵该模型精神分裂症20-23。

<table border="0" cellpadding="0" cellspacing="0" width="823">
	<tbody>
		<tr height="34">
			<td height="34" style="height:34px;width:231px;">Name of Material/ Equipment</td>
			<td style="width:153px;">Company</td>
			<td style="width:139px;">Catalog Number</td>
			<td style="width:301px;">Comments/Description</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:231px;">Behavioral Chamber Package with Retractable Levers</td>
			<td style="width:153px;">Med Associates, Inc.</td>
			<td style="width:139px;">MED-008-B2</td>
			<td style="width:301px;">Required components include two retractable levers, two stimulus lights, houselight, and reinforcement delivery system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:231px;">MED-PC software</td>
			<td style="width:153px;">Med Associates, Inc.</td>
			<td style="width:139px;">SOF-735</td>
			<td style="width:301px;"></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:231px;">MPC2XL software</td>
			<td style="width:153px;">Med Associates, Inc.</td>
			<td style="width:139px;">SOF-731</td>
			<td style="width:301px;">Data transfer utility for importing raw data into Excel format</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:231px;">Dustless precision pellets, 45 mg, sugar</td>
			<td style="width:153px;">Bio-Serv</td>
			<td style="width:139px;">F0042</td>
			<td style="width:301px;"></td>
		</tr>
	</tbody>
</table>

operant procedures for assessing behavioral flexibility in rats

行政职能包括推动规则生成和行为选择多个高层次的认知过程。这些方法的一个紧急属性以响应调整行为的变化在一个人的环境（ 即 ，行为挠性）的能力。这些过程是必不可少的正常的人类行为，并且可以在不同的神经精神的条件下，包括精神分裂症，酗酒，抑郁症，中风和阿尔茨海默氏病的干扰。了解行政职能的神经生物学已大大推进了动物的任务，以评估行为的灵活性，特别是战略转移和逆转学习分立元件的可用性。虽然一些类型的任务已被开发出来，大部分都是非自动化的，劳动密集的，并只允许一个动物的试验的时间。的自动化，操作性为基础的任务，以评估行为的灵活性的最新发展简化了工商业污水附加费婷，标准化刺激呈现和数据记录，并显着提高了吞吐量。在这里，我们描述了自动换挡策略和反转任务，利用自定义编写的软件程序来控制操作室。使用这些任务，我们已经表明，内侧前额叶皮质支配策略变速但在大鼠，类似于在人类中观察到的解离不反转学习。此外，动物新生儿海马病变，精神分裂症的神经发育模型，有选择地对受损的战略转移任务，但不能逆转的任务。策略移任务还可以单独的类型的性能错误，其中每个是归属于不同的神经基板的识别。这些自动化的任务的可用性，以及支持的独立前额区域的解离性的贡献的证据，使得它们为基本神经生物学过程的调查特别适合测定法以及博士UG发现和筛查疾病模型。

前额皮层的急性，可逆失活可以通过输注的局部麻醉剂盐酸布比卡因（0.75％，0.5微升）到前度区域的经由手术植入输注插管20在试验前约10分钟来完成。此外，灭活的过程中，可以在第一任务（"设置"），或者所述第二任务（"移位"或"逆转"）的影响，可以进行评估，以调查对学习可能一般的影响。 图2示出了这样inactivations对动物的结果执行线索对响应策略移序列。在第一天前额叶失活，所述提示/"设置"的任务，不损害性能（ 图2A），这表明内侧前额叶皮质是没有必要的初始辨别学习。然而，在第二日额叶失活，响应/"转移"的任务，signif在该动物icantly障性能所需要的显着更大的数试验，以达到标准的性能（ 图2B）的。当前额叶皮层失活，动物更加固着样的错误比在移位任务（ 图2C）从未增强的误差。这些发现复制有关内侧前额叶皮质为战略变速和重要性，特别是以前的数据，在抑制先前学习战略13,20。 相反，受过响应顺序逆转的动物并没有显示这前额叶的依赖。接收的"反转"天前额叶皮层的失活的动物并没有在任初始响应判别（ 图3A）或随后的逆转（ 图3B）20。这些发现与先前的研究一致放映盐水输注动物不同那日ê眶额皮层，而不是内侧前额叶皮质，调节逆转学习上的各种任务12,19,26，其中包括类似于这里27所描述的一个操作性的任务。 <img alt="图2" src="/files/ftp_upload/52387/52387fig2highres.jpg" /> 图2.失活的前额叶皮层损害战略移位，A，试验，以规范初始提示辨别任务（"设置"），老鼠接受生理盐水或布比卡因（补脾）的输注到在设定的日期内侧前额叶皮质。前额叶失活了最初的收购。B没有影响，试验以标准的转向响应任务（"SHIFT"）以下的盐水或布比卡因上移天的内侧前额叶输注。前额叶皮层受损失活的战略转移，以响应任务。C，错误类型犯下的动物上移一天。前换档任务（"SAL-补脾"组）额叶灭活导致增加固着样的错误。 * P &lt;0.05与生理盐水，盐水。这个数字已经被修改Floresco 等 20 <a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/52387/52387fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图3" src="/files/ftp_upload/52387/52387fig3highres.jpg" /> 图3.失活的前额叶皮层叶逆转学习完好无损。A，试验最初的反应辨别训练老鼠将随后接受生理盐水或布比卡因（补脾）的输注到内侧前额叶皮质前逆转培训期间的标准。无差异主要出现。B，试验到响应歧视的逆转过程中的标准，下面盐水或布比卡因内侧前额叶输注。前额叶灭活不损害逆转学习。这个数字已经被修改Floresco 等 20 图4给出的数据提供了如何要求使用大鼠前的战略转移可以解释数据帮助旧的规则进行"提醒"试验的一个例子。在这项研究中（Enomotor和Floresco，未发表的观察结果），将大鼠匹配对获取在第1天（ 图4A）的视觉提示规则性能。在第2天，大鼠接受了媒介物或0.2毫克/千克氟哌啶醇。在第2天测试环节开始时，他们得到20次试验，他们被要求使用获得的第1天的视觉提示规则，在此之后，规则切换中会话的响应歧视回应。如显示在图4中B，这种治疗方法在会议的前20个提醒试验损害了视觉提示规则检索。即如果我们没有用于前换档提醒试验接着，氟哌啶醇治疗的大鼠需要更少的试验，以实现标准（ 图4C），并提出少持续错误（ 图4D）上的策略改变。请注意，这些数据可以被解释由氟哌啶醇组转移的改善。但是，在该规则检索相减值表明，这些效果可以更好地理解作为障存储器的先前获得的规则，这可能导致更少的响应冲突时被要求大鼠学习一种新的规则，从而更快地移。 <img alt="图4" src="/files/ftp_upload/52387/52387fig4highres.jpg" /> 图4.受损规则检索和便利设置移诱导Haloperidol治疗，A，试验从老鼠是接受车辆（生理盐水）或多巴胺D2受体拮抗剂氟哌啶醇（0.2毫克/千克），之前的战略翌日转移序列的标准对视觉线索的歧视。两组动物表现相媲美前药物性能。B，在测试的第2天开始，大鼠接受在那里他们被要求继续使用视觉提示规则，从第一天氟哌啶醇精度显著下跌回应治疗20催试验这些提醒试验。Ç期间，提醒20后的试验，规则转向中期会议，响应歧视。需要氟哌啶醇治疗大鼠少试验的转变过程中实现的标准。D.氟哌啶醇治疗也减少了持续错误。尽管这些数据可能暗示改进的性能，在B规则检索显示减值</str翁&gt;表示表观"强化策略变速"是更可能归因于从先前获得的规则。 榎本和Floresco，未发表的观察结果降低的干扰。*，P &lt;0.05 vs.载体。 新生儿腹侧海马病变（NVHL）操纵已用于模拟大鼠28，特别是认知障碍29,30精神分裂症的一些方面。简单地说，兴奋毒性损伤给药至7天龄大鼠的海马和测试是在成人（60+天产后）。这个模型精神分裂症28的假设发展轨迹图5所示的设置移的预曝光的版本NVHL性能和对照组大鼠:响应克尤序列NVHL大鼠在未减损学习的第一条规则（响应/"设置。 "， 图5A），但显着地损害<html>在转变为新规则（提示/"移位"），通过增加达到标准（ 图5B）所需的试验次数。此外，这种逆差主要是由于增加了持续错误， 如图5C所示 ，这表明前额叶异常20,21。这些结果证实了受损的策略的先前的发现使用交叉迷宫任务29中NVHL动物移。 类似于从prefrontally灭活动物上面显示的数据，NVHL动物不损害在反转学习（ 图6A，B）中 ，虽然他们慢响应（ 图6C，D）。这种消极的发现意味着，观测到的战略转移赤字不能归因于一个简单的不能刺激21之间进行切换。 es.jpg"/&gt; 图5.设置障碍，移入精神分裂症，上设置移的NVHL序列（响应到CUE）和假对照组动物， 一个预曝光的版本性能的NVHL模式，NVHL动物在未减损响应（"设置"）的任务。B，但需要更多的显著比试验沙姆斯NVHL动物的视觉提示（"转移"）的任务。ç达到标准，就"转移"一天错误。 NVHL动物做得比假的动物更持续错误，但回归或从未增强的错误没有差异。 * P &lt;0.05与假。这个数字已经被修改Placek 等 21 <img alt="图6" src="/files/ftp_upload/52387/52387fig6highres.jpg" /> 图上的逆转学习6.缺乏NVHL减值。 <stroNG&gt; A，B，NVHL和假动物没有在他们的收购无论是最初的反应学习任务（"设置"）的能力，或响应逆转不同。C，D，NVHL动物慢于沙姆斯对应对两个"设置"和"反转"的任务。这个数字已经被修改Placek 等 21 最后，试验测试表明，动物几乎无法学习逆转提示任务， 即 ，按杠杆相对的照射光刺激。五的六只动物测试完成450逆转试验（3天）没有达到标准，和第六动物需要418试验（贝迪，未发表的观察结果;数据未显示）。这可能是因为刺激的灯光都非常显着和有吸引力的线索，使人们很难老鼠直接回应远离他们。因此，该测试序列不是RECOmmended。

Watch this Scientific Journal Video about Operant Procedures for Assessing Behavioral Flexibility in Rats at JoVE.com

Operant Procedures for Assessing Behavioral Flexibility in Rats

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 ...

operant-procedures-for-assessing-behavioral-flexibility-in-rats

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

20.7K 次观看.  St. Mary's College of Maryland. 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. 

视频: Operant Procedures for Assessing Behavioral Flexibility in Rats

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

一种新的方法为评估味质的实验室大鼠的补强性能:操作性口腔自我管理

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

科研

行为学

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

一个过程来观察大鼠巴甫洛夫空调酒精寻求行为的背景下引发的重建

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE1, and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

The goal of the protocol presented here is to describe procedures to expose rats to moderate levels of alcohol during prenatal brain development and to quantify resulting alterations in social behavior during adulthood.

适度的产前酒精暴露在成年大鼠社会行为的量化

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

鼠类精神运动警觉测试（rPVT）:一个在大鼠和小鼠的神经行为评估性能的方法

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the animal&#39;s wellbeing and health. There are numerous behavioral tests that may be applied. We selected a test for general locomotion, the open field test (OFT); a test for muscular strength, the mesh test (MT); and a test for coordination, the rotarod test (RR). Testing can be accomplished on a weekly or monthly basis. As a test for general locomotion, the OFT works by objectively monitoring movement parameters while the mouse is in an open field apparatus. The field is generally a 2&#39; x 2&#39; box, and the movements are recorded through laser sensing or through video capture. The mouse is placed in the center of the open field and allowed to move freely for the test. The MT uses the latency for a mouse to fall off an inverted screen as a measure of muscular strength. A mouse is placed on a screen, which is inverted over a clear box, and is timed for their latency to fall. Three trials are performed, with the best of the three trials scored for that day. A score of 60 s is the maximum time a mouse is left inverted. Mice are given a 5-min rest period between mesh test trials. Lastly, an accelerated protocol on the RR assesses motor coordination and endurance. During a trial, a mouse walks on a rotating rod as it increases in speed from 4 rpm to 40 rpm over 5 min. The trial ends when the mouse touches the magnetized pressure sensor upon falling. Each mouse undergoes three trials, and the best trial is scored for that day. This combined behavioral data allows for the global assessment of mobility, coordination, strength, and movement of the test animals. At least two out of the three behavioral testing measures must show improvement for an animal to qualify as having overall improved motor function.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects of a disease or treatment on an animal's wellbeing. In order to globally assess motor functioning, we selected tests for general locomotion, muscular strength, and coordination: the open field test, the mesh test, and the rotarod test, respectively.

用于评估一般运动、肌肉力量和小鼠协调性的行为测试电池

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the ...

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI.

The goal of the behavioral tests presented here is to detect functional deficits in rats after traumatic brain injury. Four specific tests are presented that detect deficits in behaviors to reflect the damage to specific brain areas at times extending to one year after injury.

颅脑损伤后大鼠行为缺陷的检测

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal&#180;s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

A wireless, bidirectional system for multi-channel neural recordings and stimulation in freely behaving rats is introduced. The system is light and compact, thus having minimal impact on the animal&#180;s behavioral repertoire. Moreover, this bidirectional system provides a sophisticated tool to assess causal relationships between brain activation patterns and behavior.

用于体内的无线双向接口记录和刺激自由行为大鼠的神经活动

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 &plusmn; 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats.

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

旋钮旋任务: 一种半自动评估大鼠前肢功能的方法

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity ...

Eye Tracking During Visually Situated Language Comprehension: Flexibility and Limitations in Uncovering Visual Context Effects

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing and the perception of the visual world. The recording of eye-gaze patterns has provided good evidence for the contribution of both the visual context and linguistic/world knowledge to language comprehension. Initial research assessed object-context effects to test&#160;theories of modularity in language processing. In the introduction, we describe how subsequent investigations have taken the role of the wider visual context in language processing as a research topic in its own right, asking questions such as how our visual perception of events and of speakers contributes to&#160;comprehension informed by&#160;comprehenders&#39; experience. Among the examined aspects of the visual context are actions, events, a speaker&#39;s gaze, and emotional facial expressions, as well as spatial object configurations. Following an overview of the eye-tracking method and its different applications, we list the key steps of the methodology in the protocol, illustrating how to successfully use it to study visually-situated language comprehension. A final section presents three sets of representative results and illustrates the benefits and limitations of eye tracking for investigating the interplay between the perception of the visual world and language comprehension.

The present article reviews an eye-tracking methodology for studies on language comprehension. To obtain reliable data, key steps of the protocol must be followed. Among these are the correct set-up of the eye tracker (e.g., ensuring good quality of the eye and head images) and accurate calibration.

视觉语言理解中的眼动追踪: 发现视觉语境效果的灵活性和局限性

The present work is a description and an assessment of a methodology designed to quantify different aspects of the interaction between language processing ...

Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is a meaningful concept because it is associated with psychiatric conditions in humans and with maladaptive behavior in non-human animals. It is believed that impulsivity is composed of separate factors. There are laboratory protocols devised to assess each of these factors using standardized automated equipment. Delay discounting is associated with the incapacity to be motivated by delayed outcomes. This factor is evaluated through intertemporal choice protocols, which consist&#160;of presenting the individual with a choice situation involving an immediate reward and a larger but delayed reward. Response inhibition deficit is associated with the incapacity to withhold prepotent responses. Differential reinforcement of low rates (DLR) and feature-negative discrimination protocols assess the response inhibition deficit factor of impulsivity. The former imposes a condition to a motivated individual in which most wait a minimum period of time for a response to be rewarded. The latter evaluates the capacity of individuals to refrain from food seeking responses when a signal of the absence of food is presented. The purpose of these protocols is to construct an objective quantitative measure of impulsivity, which serves to make cross-species comparisons, allowing the possibility of translational research. The advantages of these particular protocols include their easy set-up and application, which stems from the relatively small amount of equipment needed and the automated nature of these protocols.

We present three protocols that assess different forms of impulsivity in rats and other small mammals. Intertemporal choice procedures evaluate the tendency to discount the value of delayed outcomes. Differential reinforcement of low rates and feature-negative discrimination evaluate response inhibition capacity with and without punishment for inappropriate responses, respectively.

评估大鼠冲动不同表现的三个实验室程序

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is ...