Name: the modified hole board - measuring behavior, cognition and social interaction in mice and rats
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The authors would like to acknowledge the work of Annemarie Baars and Jos&#233; Lozeman-van &#8216;t Klooster in performing, assisting and teaching experiments using the mHB set-up.

注:实验已获得大学医学中心的乌得勒支和乌得勒支大学，荷兰的动物实验委员会。此外，动物实验遵循了实验动物保健的原则并参考准则护理和使用哺乳动物神经科学与行为研究。25 1.实验装置注意:标准MHB装置包括从辅助室（50×50×50厘米），其中，实验动物的组中配合可在测试期间被置于分离的灰色PVC实验箱（100×50×50厘米）的由一个透明的，穿孔的分区1。如果组配合的存在是不希望的，或者如果单独圈养动物进行试验，取代通过由灰色PVC的一个分区的透明的分隔（ 图1;又见奥尔等人，（2001）1）。该MHB（WI个不同的测量）用于认知测试中的协议的部分5进行说明。 <ol><li>放置板（60×20×0.5厘米;采用灰PVC）的包装盒中的中间。 注:该板可包含20气缸（ᴓ1.5厘米）14交错排列的两行或23缸（ᴓ3厘米）8交错在三线。 </li><li>由黑线周围分隔板上的区域为10个长方形（20×15厘米）和2格（20×20厘米）。 </li><li>定位板之上的舞台灯以创建板之间的光强度较大的对比度（较无保护的区域以开放场或光 - 暗过渡测试的光隔室的中心可比）和盒（保护区）为了增加电路板4,8的厌恶性质。 </li><li>房子在一个12小时的动物颠倒昼夜周期（ 如灯灭在上午7:00和灯在7:00 PM）。 注:然而，MHB也可以在传统的光时间表（见的潜在缺点讨论）1,6。 </li><li>在动物中最活跃的阶段进行行为测试（ 例如，上午10时和下午2时00分之间）4,15。 </li><li>保持2周的动物中的设施到达后一个习惯期。在此期间，有相同的人​​进行一周的行为实验处理动物4次，包括在实际的测试将被执行的所有处理程序。白天的时间只处理的动物时，动物将在后面暴露于测试。 </li><li>记录实验数据存储的视频和以优化的结果，并以降低跨观察员变异，练习使用以前的实验2的视频记录的行为打分。确保观察员执行的所有操作和程序规范。 </li></ol> 2. BEHAvioral测试 - 不配合集团的存在<ol><li>在房间里的动物经常容纳在执行行为测试（以避免运输到测试位置的可能的影响）和动物中的设施（使其习惯动物对设备的存在）到来之前安装所有的测试设备。 </li><li>拿起动物的尾巴的基地从家笼，并直接将其放置在MHB。 </li><li>将每个动物在面壁（ 如图1所示）相同的转角的装置。 </li><li>允许动物自由探索MHB一段时间（通常是5分钟1,6,16-18）。 </li><li>拥有一支经验丰富的观察者现场比分使用行为记分软件的行为参数。使用表1中列出的参数。 注:某些行为参数（ 如电机和探索行为）可能会自动为如得分， </em&gt;（2010年）19后MHB必要的调整，亨利等人讨论。 </li><li>为了避免基于嗅觉暗示偏压每次试验后清理用自来水和纸巾的装置。 注:测试社会安置动物时可能测试阶作用，应牢记17,20。 </li></ol> 3.行为测试 - 在小组配合的存在<ol><li>在组壳体的情况下，测量与实验动物和测试期间其保持架配合的相互作用。 <ol><li>放置组配合在该组隔室的实验动物试验之前，以允许习惯（主要是10-30分钟1,12）。 注:社会应激条件下的测试，可以通过测试一个社会个体击败13时，将主导笼队友在小组车厢。 </li><li>将实验动物在测试隔室，并允许它以释放LY探索MHB在第2节。 注:测试社会安置动物时可能测试阶作用，应牢记17,20。 </li><li>拥有一支经验丰富的观察者现场比分使用行为记分软件的行为参数。使用表1中列出的参数。 </li><li>为了避免基于嗅觉暗示偏压每次试验后清理用自来水和纸巾的装置。 </li></ol></li></ol> 4.新物体识别和食物摄入量抑制<ol><li>熟悉的动物对象（例如一个骰子或食品粒料）在他们的家笼，实验前2天。 </li><li>从在从起点的角跨越一个新的物体（例如螺栓或不熟悉的食品）将熟悉物体在装置相距2厘米。 </li><li>测量动物需要接近小说和熟悉对象/食物的时间。使用的参数中&lt;STRONG&gt;表1。 </li><li>为了避免基于嗅觉暗示偏压每次试验后清理用自来水和纸巾的装置。 </li></ol> 5.认知测试<ol><li>用于测试的大鼠3,22放置一个较小的电路板（35×22×1厘米）10缸中的框的中部（ 图1）。减少大小为50×50厘米框插入制成的灰色PVC的分区检测小鼠21。 </li><li>气味所有气缸有味道的动物被吸引到（ 例如香草）和奖励（ 例如，一块杏仁，一个非常可口奖励小鼠和大鼠）网格下饵都让动物无法将其删除。 </li><li>提示缸（通常3）用五色环（带有灰色PVC对比），并引诱他们一个可拆卸的奖励（ 如 0.05克一块杏仁）。 </li><li>在实验前，熟悉日常在2天的奖励动物他们的家笼用的镊子提供，并确保动物吃。 </li><li>拥有一支经验丰富的观察者现场比分使用行为记分软件的行为参数。测量与所述例外识别物体或食物摄取抑制相关的参数，除了在第2（ 表1）中提到的行为参数在表2中列出的参数。 </li><li>阶段1:对于每个动物，每天进行四个试验具有恒定 ​​审间间隔（ 例如，30-60分钟），直到一个恒定的时间来完成试验达到（ 即，当所有三个杏仁片已经被收集）。 </li><li>第2阶段:提示和鱼饵三种不同的汽缸，然后将动物在设置四个试验，以测试逆转学习能力。 </li><li>为了避免基于嗅觉暗示偏压每次试验后清理用自来水和纸巾的装置。 </li></ol>

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The authors have nothing to disclose.

该MHB范例可以用于测量无条件行为多个维度。该协议可以根据实验的目的略有改变。在这个协议中，我们讨论的设置，时间和测量通常是在我们的实验室中使用。然而，轻微的偏差，以该装置的测量已被用于在过去和也在板气缸的量可以变化3。经常研究使用，每试验5分钟的测试时间，但其他的测试时间也可以是适当的， 即，一旦结束测试的认知试验已成功，或延长测试时间完成，如果动物是非常急或身体受损。测试一天的时间被选定为红光下条件，因为老鼠是夜行性动物，是最活跃的早期黑暗阶段。 Roedel 等人（2006）示出了光或黑暗阶段测试对行为和认知性能的影响在DBA小鼠的MHB 16。其他的研究已经进行在白光条件1,6- MHB实验，然而，应当注意的是，在白光下的条件测试可诱导行为抑制和认知中断（如图DBA小鼠）16。 表1和2含有待测量的大量的行为参数。在数据分析期间，这可能导致一些参数，指示例如"延迟到第一引入板&#39;的显著增加，但不是在同一激励系统的其它参数（在这种情况下，"避免&#39;）。在某些情况下，这可能会导致不确定的结果。 GUILLOUX 等人（2011）介绍了集成行为z得分的行为表型在小鼠24上 。与使用综合行为z得分的多个参数可被组合到单个z得分描述特定motivati​​o最终系统。随后的z分数可以在轮到自己更轻松地在行为测试和实验对比。 除了 ​​这种模式的描述的特征，更深刻的使用成为Salomons 等人的研究清楚。（2012）。习惯化的两个小鼠品系（BALC / CJ和129P3 / J），在MHB新颖性进行了比较，显示出在行为灵活性差表示129P3 / J小鼠4的非自适应行为简档，镜像受损适应能力和可能甚至病态的焦虑。 最后，该MHB允许多个行为层面在一次实验中测量。通过从传统孔板和开放现场测试，无条件的行为，社会交往，认知和适应能力， 即结合的特点，福利可以进行调查。该测试可以例如用于评估由于行为变化到pharmacological-和/或遗传操作，选育和适应能力。相较于传统的测试电池，所需要的动物的数量明显减少，应力测试期间所经历的动物是非常低的。

改性孔板（MHB）被用来评估的无条件行为多个维度，主要是在小鼠和大鼠1。一些广泛使用的测试测量单个行为参数，它不完全覆盖一个行为尺寸的整个表型。该MHB是基于鼠类可以展示自己丰富的行为库只有在丰富的测试环境2，从而使复杂的行为学观察的概念开发的。 该组式包括传统孔板和旷场试验的特性，从 ​​而导致一个复杂的单个范例，它克服一个试验电池的缺点（ 即在减少动物的数量用1,3,4，绕过测试顺序5，减少时效和成本6）可能产生的影响。与大多数行为测试（ 例如，Hånell＆Marklund，2014年）7 &lt;/ SUP&gt;时，MHB的一个优点是，动物不需要是食物剥夺以增加的动力来解决的任务。此外，社会隔离，可以在测试过程中通过放置在一个（胺基）隔室由透明多孔隔板从测试室中分离的实验动物的组配合，允许视觉，听觉和嗅觉接触8,9-规避。 该MHB已（药理学）验证对小鼠和大鼠1,6。大范围的行为可以测量，如回避行为，风险评估，觉醒，探索，自主活动，习惯，社会亲和力和认知2,8-10。此外，该MHB可以与食物摄取抑制试验，以及新物体识别测试10,11相结合。最后，该MHB也可以使用通过测试社会败动物，同时将一个主导个体中进行社会应力实验组车厢12,13。这个协议对小鼠和大鼠将给MHB的多个应用程序的概述。

<table><tbody><tr><td>Cognitive mHB apparatus</td><td></td><td></td><td>The box for cognitive testing is 50x50 cm by inserting a partition made of grey PVC in the standard mHB. A smaller board (35x22x1 cm) with 10 cylinders is placed in the middle of the box. All cylinders are scented with a flavor animals are attracted to (e.g. vanilla) and all are baited with a reward (e.g. a piece of almond) beneath a grid so the animals cannot remove it. Cylinders (often three) are cued with a colored ring (contrasting with the grey PVC) and are baited with a removable reward (e.g. 0.05 g piece of almond).&amp;nbsp;</td></tr><tr><td>Vanilla flavor</td><td></td><td></td><td>Vanilla flavor dissolved in water (0.02%)</td></tr><tr><td>Camera</td><td></td><td></td><td>Camera that generates sufficient quality output to rescore the behavior from video.&amp;nbsp;</td></tr><tr><td>Stage light</td><td></td><td></td><td>A theather light that allows to adjust the light intensity and the dimensions of the surface that is lit.&amp;nbsp;</td></tr><tr><td>Behavioral scoring software</td><td></td><td></td><td>Behavioral scoring software.</td></tr></tbody></table>

the modified hole board - measuring behavior, cognition and social interaction in mice and rats

这个协议描述了改性孔板（MHB），它结合特征从传统孔板和旷场并且被设计来测量无条件行为在小型实验室哺乳动物（ 例如，小鼠，大鼠，树鼩和小灵长类）的多个方面。这种模式是一种使用一个行为测试电池的一个有价值的替代，因为动物的行为简档的宽光谱行为可以在一个单一的测试进行调查。 该装置由一个盒子，代表着"保护"区域中，从一组室分离。甲板，在其上小圆柱体交错排列在三条线，被放置在盒的中心，代表的设置了"无保护的"区域。动物的认知能力可以通过引诱一些钢瓶在董事会和测量工作，并参考内存进行测量。其他无条件的行为，如activitY型所关乎，焦虑所关乎社会的行为，可以用这种模式来观察。行为的灵活性和使其习惯一种新颖的环境的能力，可以另外通过使动物在MHB多次试验，揭示洞察动物的适应能力进行观察。 由于在一个行为测试电池测试阶效应，幼稚的动物应该用于每个单独的实验。通过在一个单一的范例测试多个行为层面并由此避开这个问题，所使用的实验动物的数量减少。此外，通过避免在测试过程中，没有必要食物社会隔离剥夺的动物中，MHB表示一个行为测试系统，诱导如有应力的量非常低。

大量的参数，可以在MHB来测量使该设置特别适用于测量众多行为层面。其中一个例子是行为适应的鉴定到一种新的环境通过重复暴露于测试。 。Salomons等 （2010）研究了小鼠（BALB / CJ和129P3 / J）的MHB两个近交系的习惯在两个不同的光照条件下（红灯:45勒克斯与白光:框和板之间的对比:框和板之间的对比:115勒克斯（另见协议第1.3节））4。 BALC / cJ小鼠显示减少（habituating）延迟，直到第一板条目（见表1）在红光条件下， 如图2A所示 。与此相反，129P3 / J小鼠表现出习惯的迹象了试验。 图2B显示在白色光线条件下的实验。 BALB / cJ小鼠再显示一个减小延迟到第一板条目以上试验尽管该一nimals显示较慢的习惯模式相比，红光条件。 129P3 / J小鼠不仅显示再次受损习惯，也是白色光的条件下向致敏的趋势。同样地，在一项研究Salomons（2012）129P2 / OlaHsd小鼠显示受损的行为灵活性响应于新颖相比只BALB / cOlaHsd小鼠23。在习惯能力的不同，当在MHB 4测试也因此成为小鼠两个近交系之间的明显。 认知版本的MHB的可以例如被用于测量认知损伤的小鼠。范德Kooij 等 。 （2010年）中使用这种设置来测量C57BL / 6J小鼠轻度脑缺氧缺血的认知功能（缺氧45分钟; HI-45），严​​重的HI（75分钟缺氧; HI-75）和sham-对照组小鼠9。完成试验的能力（ 即，发现在5分钟内的饵孔）示于图3A。 </stroNG&gt;的短期记忆失误数（重温了饵孔），长期记忆错误（访问非饵孔）和遗漏错误（没有访问被逼急的孔）， 如图3B-D分别。 为了证实对HI-45组无认知损伤，这组抗假控制在反转任务测试。三饵孔被任命为三个不同的汽缸和动物测试4项试验。第一阶段的最后试验用的反转级的第一试验比较时的逆转作用变得很明显。完成4逆转试验的持续时间给出的指示对整体性能。 图4示出的等待时间，完成试验为两组，并明确整体治疗效果是明显的。这意味着，在逆转的任务的确有认知灵活性（重新学习）在HI-45组的这是一个障碍<html>使用MHB 9来检测。 <img alt="图1" src="/files/ftp_upload/52529/52529fig1.jpg" /> 图修改后的孔板1示意图。 （一）设置了由一个测试盒（箱）与在（无保护）董事会表示有锯齿线和组车厢中间。 <img alt="图5" src="/files/ftp_upload/52529/52529fig5.jpg" /> =新物体， <img alt="图6" src="/files/ftp_upload/52529/52529fig6.jpg" /> =熟悉的对象， <img alt="图7" src="/files/ftp_upload/52529/52529fig7.jpg" /> =起点。（B）的认知版本改性孔板的小鼠的示意图概述。气缸（C）的侧视图中认知版本改性孔板的使用。一块杏仁放在所有气缸的网格下方。目标="_空白"&gt;点击此处查看该图的放大版本。 <img alt="图2" src="/files/ftp_upload/52529/52529fig2.jpg" /> 图2.红色光或白色光的条件。 （A）延迟，直到第一次董事会记录（指+ SEM）BALB / CJ，并在红光条件下（0-5盒勒克斯和板45勒克斯）测量123P3 / J小鼠。重复测量ANOVA与Huyn-Feldt调整透露的应变（P = 0.025），试验（P &lt;0.001），试验X应变的相互作用（P &lt;0.001）效果事后分析:菌株之间:* = P &lt;0.0026之间连续两个试验:$ = P &lt;0.0026（BALB / CJ）（B）第一板条目的潜伏期（平均+ SEM）在白光条件（盒0-5勒克斯和电路板120勒克斯）。重复测量ANOVA与Huyn-Feldt调整透露的应变（P = 0.031），试验（P &lt;0.001），试验X应变的相互作用（P &lt;0.001）EFFE。克拉事后分析:* = P &lt;0.0026，连续两次试验之间:$ = P &lt;0.0026（BALB / CJ）和T = P &lt;0.0026（123P3 / J）菌株之间。这个数字已经被修改Salomons 等人 2010年4月。 <a href="https://www.jove.com/files/ftp_upload/52529/52529fig2highres.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/52529/52529fig3.jpg" /> 在MHB图3.认知测试（阶段1）。所有的数字显示平均+ SEM（A）的潜伏期，完成假对照组小鼠的试验（秒），HI-45和HI-75（B）遗漏错误数，（C）非饵孔互访和（D）重访的诱饵孔。 * = P &lt;0.05，** = P &lt;0.01，*** = P &lt;0.001假与HI-75，＃= P &lt;0.05，## = P &lt;0.01，### = P &lt;0.001HI-45与HI-75。这个数字已经被修改范德Kooij 等人，2010年9。 <a href="https://www.jove.com/files/ftp_upload/52529/52529fig3highres.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图4" src="/files/ftp_upload/52529/52529fig4.jpg" /> 图4.逆转学习任务（第2阶段）。延迟完成试验（秒），在逆转学习任务（平均+ SEM）。试用效果:＃= P &lt;0.05，## = P &lt;0.01（一审逆转的任务与以往的审判）。治疗效果:* = P &lt;0.05，** = P &lt;0.01（HI-45与假）。这个数字已经被修改范德Kooij 等人，2010年9。 <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> 系统 </td><td> 活动 </td><td> 测得的参数 </td></tr><tr><td> AVOidance </td><td>进入董事会</td><td>频率，延迟（S），持续时间（％）和平均持续时间（S）在董事会</td></tr><tr><td>风险评估</td><td>拉伸出席</td><td>频率和延迟时间（S）伸展身体姿势（包括后肢） </td></tr><tr><td>觉醒</td><td>宠物美容</td><td>频率，延迟（多个），持续时间（％）和平均持续时间（S）的自修饰</td></tr><tr><td></td><td>排便</td><td>频率和薄利的潜伏期（S）生产</td></tr><tr><td></td><td>排尿</td><td>频率和排尿的潜伏期（S） </td></tr><tr><td>导演探索</td><td>孔探访</td><td>频率和汽缸访问延迟（S） </td></tr><tr><td></td><td>新物体的探索</td><td>频率，延迟（多个），持续时间（％）和平均持续时间（S）探索新物体</td></tr><tr><td>无方向的探索</td><td>饲养箱&lt;/ TD&gt; <td>频率和后脚站起的潜伏期（S）在框中（前爪不碰墙） </td></tr><tr><td></td><td>饲养板</td><td>频率和后脚站起的潜伏期（S）在董事会</td></tr><tr><td></td><td>孔探</td><td>频率和汽缸探索的潜伏期（S） </td></tr><tr><td>记忆</td><td>熟悉对象的探索</td><td>频率，延迟（多个），持续时间（％）和平均持续时间（S）探索熟悉的物体</td></tr><tr><td>社会亲和力</td><td>小组互动</td><td>频率，延迟（多个），持续时间（％）和平均持续时间（S）与该组隔室相互作用</td></tr><tr><td>自主活动</td><td>线路穿越</td><td>次数的越线延迟（S） </td></tr></tbody></table> 表1:行为参数一览 <table border="0" cellpadding="0" cellspacING ="0"&gt; <tbody><tr><td> 内存系统 </td><td> 参数 </td><td> 描述 </td></tr><tr><td> 长期记忆 </td><td>错误的选择</td><td>参观非饵缸;鼻子边缘下方</td></tr><tr><td> 遗漏错误 </td><td>一个诱饵缸遗漏</td><td>没有访问一个诱饵缸</td></tr><tr><td> 短期记忆 </td><td>重复的选择</td><td>重温到开涮缸;鼻子边缘下方</td></tr><tr><td> 整体表现 </td><td>总的试用时间</td><td>时间，直到所有开涮缸已被访问</td></tr></tbody></table> 表2:认知参数一览

Watch this Scientific Journal Video about The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats at JoVE.com

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

修改后的孔板 - 测量行为，认知和社会互动小鼠和大鼠

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

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Behavior

17.7K 次观看.  Utrecht University. This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities. 

视频: The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the &#34;cloud&#34; and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in&#160;cabinet; two such cabinets (16 environments) may be controlled by one computer.

Fully automated system for measuring physiologically meaningful properties of the mechanisms mediating spatial localization, temporal localization, duration, rate&#160;and probability estimation, risk assessment, impulsivity, and the accuracy and precision of memory, in order to assess the effects of genetic and pharmacological manipulations on foundational mechanisms of cognition in mice.

小鼠自动化，定量认知/行为筛选：对于遗传学，药理学，动物认知与本科教学

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and ...

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行为学

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

Prolonged and comprehensive monitoring of mice in a home-cage environment provides a deeper understanding of aberrant behavior in murine models of brain diseases. This paper describes the Integrated Behavioral Station (INBEST) as the key component of contemporary behavioral analysis.

小鼠疾病模型的集成行为车站行为表型（INBEST）

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of ...

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the test mouse is placed in a standardized apparatus and relevant behaviors are assessed in three different sessions (called session I, II, and III).
The apparatus has three compartments (see Figure 1), the left and right compartments contain an inverted cup which can house a mouse (called &#34;stimulus mouse&#34;).
In session I, the test mouse is placed in the cage and its mobility is characterized by the number of transitions made between compartments. In session II, a stimulus mouse is placed under one of the inverted cups and the sociability of the test mouse is quantified by the amounts of time it spends near the cup containing the enclosed stimulus mouse vs. the empty inverted cup. In session III, the inverted cups are removed and both mice interact freely. The sociability of the test mouse in session III is quantified by the number of social approaches it makes toward the stimulus mouse and by the number of times it avoids a social approach by the stimulus mouse.
The automated evaluation of the movie detects the nose of the test mouse, which allows the determination of all described sociability measures in session I and II (in session III, approaches are identified automatically but classified manually). To find the nose, the image of an empty cage is digitally subtracted from each frame of the movie and the resulting image is binarized to identify the mouse pixels. The mouse tail is automatically removed and the two most distant points of the remaining mouse are determined; these are close to nose and base of tail. By analyzing the motion of the mouse and using continuity arguments, the nose is identified.
<img alt="Figure 1" src="/files/ftp_upload/52508/52508fig1.jpg" /> 
Figure 1. Assessment of Sociability During 3 sessions. Session I (top): Acclimation of test mouse to the cage. Session II (middle): Test mouse moving freely in the cage while the stimulus mouse is enclosed in an inverted cup. Session III (bottom): Both test mouse and stimulus mouse are allowed to move freely and interact with each other.

This protocol describes a method to quantify mouse sociability. Mice are videotaped as they move and interact in a special cage. Movie processing allows for the automated quantification of sociability with excellent accuracy and reliability.

使用自动图像处理方法鼠标社交性的实验评估

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the ...

Assessment of Social Interaction Behaviors

Social interactions are a fundamental and adaptive component of the biology of numerous species. Social recognition is critical for the structure and stability of the networks and relationships that define societies. For animals, such as mice, recognition of conspecifics may be important for maintaining social hierarchy and for mate choice 1.
A variety of neuropsychiatric disorders are characterized by disruptions in social behavior and social recognition, including depression, autism spectrum disorders, bipolar disorders, obsessive-compulsive disorders, and schizophrenia. Studies of humans as well as animal models (e.g., Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, Rattus norvegicus) have identified genes involved in the regulation of social behavior 2. To assess sociability in animal models, several behavioral tests have been developed (reviewed in 3). Integrative research using animal models and appropriate tests for social behavior may lead to the development of improved treatments for social psychopathologies.
The three-chamber paradigm test known as Crawley's sociability and preference for social novelty protocol has been successfully employed to study social affiliation and social memory in several inbred and mutant mouse lines (e.g. 4-7). The main principle of this test is based on the free choice by a subject mouse to spend time in any of three box's compartments during two experimental sessions, including indirect contact with one or two mice with which it is unfamiliar. To quantitate social tendencies of the experimental mouse, the main tasks are to measure a) the time spent with a novel conspecific and b) preference for a novel vs. a familiar conspecific. Thus, the experimental design of this test allows evaluation of two critical but distinguishable aspects of social behavior, such as social affiliation/motivation, as well as social memory and novelty. "Sociability" in this case is defined as propensity to spend time with another mouse, as compared to time spent alone in an identical but empty chamber 7. "Preference for social novelty" is defined as propensity to spend time with a previously unencountered mouse rather than with a familiar mouse 7. This test provides robust results, which then must be carefully analyzed, interpreted and supported/confirmed by alternative sociability tests. In addition to specific applications, Crawley's sociability test can be included as an important component of general behavioral screen of mutant mice.

Here we describe a detailed protocol for examination of sociability in mice by using Crawley's sociability and preference for social novelty test. We describe the advantages and possible applications for this procedure, including critical details important for correct interpretation of the results.

社会交往行为的评估

Social interactions are a fundamental and adaptive component of the biology of numerous species. Social recognition is critical for the structure and ...

神经科学

Quantifying Social Motivation in Mice Using Operant Conditioning

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered shuttle boxes were equipped with two operant levers (left and right) and a food receptacle in one chamber, which was then divided from the second chamber by an automated guillotine door covered by a wire grid. Different stimulus mice, rotated across testing days, served as a social stimulus behind the wire grid, and were only visible following the opening of the guillotine door. Test mice were trained to lever press in order to open the door and gain access to the stimulus partner for 15 sec. The number of lever presses required to obtain the social reward progressively increased on a fixed schedule of 3. Testing sessions ended after test mice stopped lever pressing for 5 consecutive minutes. The last reinforced ratio or breakpoint can be used as a quantitative measure of social motivation. For the second paradigm, test mice were trained to discriminate between left and right lever presses in order to obtain either a food reward or the social reward. Mice were rewarded for every 3 presses of each respective lever. The number of food and social rewards can be compared as a measurement of the value placed upon each reward. The ratio of each reward type can also be compared between mouse strains and the change in this ratio can be monitored within testing sessions to measure satiation with a given reward type. Both of these operant conditioning paradigms are highly useful for the quantification of social motivation in mouse models of autism and other disorders of social behavior.

This article describes a new protocol for the quantitative measurement of social motivation in mice using operant conditioning for a social reward. The protocol is useful for the measurement of social motivation in mouse models of autism and other disorders of social behavior.

量化的社会动机小鼠使用操作条件反射

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered ...

Assessing Burrowing, Nest Construction, and Hoarding in Mice

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented.
Burrowing was first developed in Oxford13. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them.6



Food pellets are not an essential substrate for burrowing; mice will empty tubes filled with sand, gravel, even soiled bedding from their own cage. Moreover, they will empty a full tube even if an empty one is placed next to it8.



Several nesting protocols exist in the literature. The present Oxford one simplifies the procedure and has a well-defined scoring system for nest quality5. 



A hoarding paradigm was later developed in which the mice, rather than hoarding back to the real home cage, were adapted to living in the "home base" of a hoarding apparatus. This home base was connected to a tube made of wire mesh, the distal end of which contained the food source. This arrangement proved to yield good hoarding behaviour, as long as the mice were adapted to living in the "home base" during the day and only allowed to enter the hoarding tube at night.

Burrowing, nesting, and hoarding are species-typical activities that mice readily perform in the laboratory. This article describes how they can be easily and cheaply assessed. These protocols are extremely sensitive to mouse strain, brain lesions and diseases. Moreover they constitute &#x201C;environmental enrichment&#x201D; for the mice, and embody the &#x201C;Refinement&#x201D; aspect of the &#x201C;3 Rs&#x201D;18.

评估挖洞，在小鼠的鸟巢建设和囤积

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening ...

Analyzing Spatial Learning and Prosocial Behavior in Mice Using the Barnes Maze and Damsel-in-Distress Paradigms

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. The Barnes maze can also assess other mouse behaviors, such as general motivation to escape from the maze platform and exploratory behavior. The Barnes maze can measure whether a genetic mutation or environmental variable can impact the acquisition and retention of spatial memories, as well as provide information about the search strategy employed by the mice. Here we use the Barnes maze to detect a memory deficit in adult mice following a single developmental ethanol exposure event. The newly described Damsel-in-Distress paradigm exposes a male mouse to a female mouse trapped in a chamber in the open center field of the arena. It provides an opportunity for the mouse to socially respond to the trapped female and exhibit prosocial behavior. The Damsel-in-Distress paradigm can also be used to examine mouse behavior in a novel arena and measure locomotor activity. Both the Barnes Maze and the Damsel-in-Distress protocols require minimal financial investment and most aspects of the tests can be constructed from common lab supplies. These flexible and accessible tools can also be used to detect behavioral changes over the course of development.

This protocol measures spatial learning and memory using the Barnes maze. A novel Damsel-in-Distress paradigm is used to assess locomotor activity and prosocial behavior in mice.

利用巴恩斯迷宫和困境中的破坏范式分析小鼠的空间学习和社会行为

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. ...

A Behavioral Test Battery for the Repeated Assessment of Motor Skills, Mood, and Cognition in Mice

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and dysfunctions in mood and cognition are common and often shared symptoms in neurodegenerative diseases. Shown here is a behavioral test battery for motor, mood, and cognition, which can be repeatedly tested in a longitudinal study. This battery assesses the overall behavioral phenotype in mice by examining each domain of behavior with at least two independent well-accepted tests (i.e., open-field test and rotarod test for motor function, social interaction test, elevated plus maze test, and forced swim test for emotional function, and Morris water maze test and novel object recognition test for cognitive function). Therefore, this sensitive and comprehensive test battery is a powerful tool for the study of behavioral alternation in neurodegeneration.

A comprehensive behavioral test battery of motor skills, mood&#8212;including social interaction, depression, and anxiety&#8212;and cognition is designed for the repeated assessment of neurodegeneration-related behavioral changes in mice.

一种用于小鼠运动技能、情绪和认知重复评估的行为测试电池

Pharmacological and toxicological studies in neurodegeneration require comprehensive behavioral analysis in mice because motor dysfunctions and ...

A System for Tracking the Dynamics of Social Preference Behavior in Small Rodents

Exploring the neurobiological mechanisms of social behavior requires behavioral tests that can be applied to animal models in an unbiased and observer-independent manner. Since the beginning of the millennium, the three-chamber test has been widely used as a standard paradigm to evaluate sociability (social preference) and social novelty preference in small rodents. However, this test suffers from multiple limitations, including its dependence on spatial navigation and negligence of behavioral dynamics. Presented and validated here is a novel experimental system that offers an alternative to the three-chamber test, while also solving some of its caveats. The system requires a simple and affordable experimental apparatus and publicly available open-source analysis system, which automatically measures and analyzes multiple behavioral parameters at individual and population levels. It allows detailed analysis of the behavioral dynamics of small rodents during any social discrimination test. We demonstrate the efficiency of the system in analyzing the dynamics of social behavior during the social preference and social novelty preference tests as performed by adult male mice and rats. Moreover, we validate the ability of the system to reveal modified dynamics of social behavior in rodents following manipulations such as whisker trimming. Thus, the system allows for rigorous investigation of social behavior and dynamics in small rodent models and supports more accurate comparisons between strains, conditions, and treatments.

Described here is a novel automated experimental system that offers an alternative to the three-chamber test and also solves several caveats. This system supplies multiple behavioral parameters that enable rigorous analysis of small rodent behavioral dynamics during the social preference and social novelty preference tests.

跟踪小啮齿动物社会偏好行为动态的系统

Exploring the neurobiological mechanisms of social behavior requires behavioral tests that can be applied to animal models in an unbiased and ...

<meta charset="utf8"></head><body>小鼠模型中自闭症谱系障碍的行为检测

Strategies for Assessing Autistic-Like Behaviors in Mice

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).

<meta charset="utf8"></head><body>评估小鼠自闭症样行为的策略

Rodent models are valuable tools for studying core behaviors related to autism spectrum disorder (ASD). In this article, we expound on two behavioral tests for modeling the core features of ASD in mice: self-grooming, which assesses repetitive behavior, and the three-chamber social interaction test, which documents social impairments.

评估小鼠自闭症样行为的策略

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social ...