威康信托基金会提供开放存取资金牛津大学。罗伯特·迪肯资助，由威康信托基金资助WT084655MA牛津OXION组的成员。

<html> 1。牛津嬉水池嬉水池已连续三次设计，MK 1-3。全部采用浅（2厘米）所含水分的白色（加强其aversiveness）的基础，这是由透明的有机玻璃或透明的丙烯酸塑料制成的墙壁包围。这些有真/假退出设置在其中。假出口被遮挡的黑色木塞，而​​真正的出口是开放和加入一个黑色的塑料管，用鼠标里面可以拆除。鼠标，然后返回其家笼而管内的迅速和无损伤。首次出版后的嬉水池，据报道，返回家笼也是一种有效的激励学习拉什利III迷宫2。 阿水温度为20-25°C。 20-21°C是理想的，它已经注意到，一些老鼠似乎动力不足，在较高的温度下。 内容“&gt;第一个迷宫5呈圆形，然而，有时老鼠（尤其是那些与海马病变）似乎没有注意到开放的出口管的八角形设计，放置在弯道的出口管，以吸引小鼠的注意，极大地改善此问题，然而，在偶然的错误率性能。将4/trial，而不是到6/trial与管12的圆形设计，因此，十二角形池中有11个假，1是现在使用真正的出口的角度设置在路口的墙壁。 1.1。嬉水池的演变和特点可1：圆形池85厘米，直径12的真/假退出（ 图1）。 MK 2：八角池86厘米，直径8真/假出口设置在弯道。 MK 3：十二次（12面），游泳池，120厘米，直径12真/假出口玉米ERS（ 图4）。 在上述所有的（和划动的Y-迷宫，见下文）的出口管为直径40毫米。然而，它偶尔会感觉到，老鼠都不愿意进入这些，和Y-迷宫的控制性能有时会沾后，他们一直反应良好。因此，考虑到他们是多么容易进入穴居设备（见朱庇特出版“评估穴居，巢建设和囤积在小鼠”），也巴恩斯迷宫的出口孔直径50毫米，有人认为，如果40毫米太小。在家里笼六C57BL / 6小鼠进行的测试。 （他们似乎更愿意在家里笼进入40毫米管想必压力较低，在这里比在一块设备，这样在家里笼测试将减少入境差异较小的管略有厌恶，使得测试较为保守）。两个40毫米管和两个50毫米管被放置在地板上，在一个交替模式。据预测，有更多的项目（9项）超过40毫米到50毫米的管（28项）。因此，试点计划用50毫米的出口管上一个新的Y型迷宫，如果这是成功的的十二次游泳池和戏Y-迷宫老40毫米管将被替换为新的50毫米的。 作为嬉水池，戏Y-迷宫和Y-迷宫空间新奇，依靠鼠标设备通过透明墙壁看到房间的线索，所有的空间试验室应布置具有鲜明的线索（如货架，橱柜，墙壁上的黑色塑料的形状）。 2。运行嬉水池<ol><li>鼠标放置在中心的游泳池，相对的四个位置上的周边（9，12点或3点，如果转义管是位于6点钟位置）。位置是半随机的三个连续的试验最多可以在同一个方向。这可以是在实践中难以实现的，因为作为学习进行小鼠往往确定自己的方位朝向正确的退出，降低入池，因为它们的尾巴。如果他们这样做是坚决不应该尝试迫使他们计划中的位置，因为他们简单地展示了学习。 </li><li>释放他们时，他们只是在水面上，然后他们放弃，即刻知道，他们不再举行。慢慢地释放他们的结果在他们的努力释放自己，这可以削弱初始方向。这也适用于划动的Y-迷宫。 </li><li>最大试验长度为60秒。如果鼠标无法逃脱然后，手动引导它到出口采用透明有机玻璃桨一对夫妇的约30×20厘米，每个测量。所采取的措施的时间找到出口（定义：所有的头管内）和错误。被定义为一个头的长度（包括真正的退出）从管内的错误。传递真正的退出，没有入门，我一般发生nfrequently后的前几个试验。可以说，虽然这是一个问题，另一种观点是空间认知受损的小鼠做到这一点，因为他们不知道有一个出口，周围有。控制知道的，因此更充分的调查。在分析中的错误的数量，施加于天花板的11个错误/试，以防止过多的数据歪斜。这将减轻对空间受损的老鼠被发现在赤字， 也就是说 ，它是一个保守的措施。失败的小鼠在60秒内到达出口被分配该试验的得分为11个错误。因此，60秒的时间总是有11个错误。 </li></ol> 3。杖刑的Y-迷宫为了简化嬉水池的程序，并决定用Y-迷宫实验设备，根据同样的原则作为嬉水池操作。该装置由三个臂透明聚苯乙烯或有机玻璃制成的，每次30×8×20厘米。这是个装在一个白色的底座（ 图7）。选择白色，最大化地板颜色aversiveness和鼓励逃离由浅（深2厘米）。至于在水迷宫中，只有一个真正的出口处，与其他两个臂终止于假退出看起来是相同的（ 图8）内的迷宫。 运行划桨Y-迷宫鼠标放置在闭合臂的端部，朝向远离中心。武器选择作为起始位置的序列被定义为一个半随机序列;不超过三个连续试验具有相同的位置，并且数目相等的左侧或右侧臂。每次试验持续60秒。如果鼠标无法退出（全出口管头），在这段时间内，鼓励它进入臂借助一块透明的有机玻璃。退出臂的基地由有机玻璃被封锁，并允许鼠标​​本身找到出口;应鼓励更好的学习比推入管。但是，这可能需要使出如果鼠标不愿意进入管内后，15秒。采取措施退出的总时间和错误的数量（不含尾巴全身进入盲臂）。 评分划桨Y-迷宫正确的审判有两种定义：首先鼠标&lt;60秒，找到了出口，没有进入盲武器，被砍下的错误，如果盲目的武器输入和/或出口处没有发现在60秒。这种分析混淆故障开始移动手臂条目中的错误。其次，一个劲儿强调认知能力的分析，可以通过排除，每个鼠标，鼠标在60秒内没有离开起始臂的所有试验，（ 即删除所有0 +60分数），然后计算正确的％剩余的试验。 4。两种类型的Y-迷宫结合 1。设备当建立一个嬉水Y-迷宫，它是有用的，把两扇门，使其能够运行（干）新奇的空间记忆实验6（ 图13）。闸门的透明覆盖出口孔的出口臂在端壁，而不透明的闸门可以插入一个臂密封，在采样过程中从其他两个阶段的测试。重要的是，这些门是跑步者不在范围内的老鼠，否则他们可能会分散他们的注意力，因为它们会出现潜在的逃生路线。在理想的情况下，他们应该延长7厘米，从迷宫墙的顶部。 2。设置放置在地板上的Y-迷宫木片铺垫材料的薄层（0.5厘米）。重新分配个别小鼠两者之间的测试阶段，和老鼠之间。最佳实践，为使嗅觉环境MO第一对随后的老鼠，放一个或两个非实验小鼠在迷宫中，在实验开始前几分钟重新类似。 3。程序随着出口手臂挡着不透明门，透明门阻止其退出孔，鼠标放置在起始臂（两个非出口武器的迷宫），并允许它来探索5分钟。然后将其删除，提高不透明门，允许访问所有三个武器，取代它起始臂，观察2分钟。注意的条目数和每个臂中花费的时间。控制老鼠应该记得，前两个武器，并花更多的时间在以前无法进入的手臂。

<ol>
	<li>Barnes, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Memory+deficits+associated+with+senescence:+a+neurophysiological+and+behavioral+study+in+the+rat.">Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat.</a> J. Comp. Physiol. Psychol. 93, 74-104 (1979).</li><li>Blizard, D. A., Cousino Klein, L., Cohen, R., McClearn, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Novel+Mouse-Friendly+Cognitive+Task+Suitable+for+Use+in+Aging+Studies.">A Novel Mouse-Friendly Cognitive Task Suitable for Use in Aging Studies.</a> Behav. Genetics. 33, 181-189 (2003).</li><li>Deacon, R. M. J., Cholerton, L. L., Talbot, K., Nair-Roberts, R. G., Sanderson, D. J., Romberg, C., Koros, E., Bornemann, K. D., Rawlins, J. N. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-dependent+and+-independent+behavioral+deficits+in+Tg2576+mice.">Age-dependent and -independent behavioral deficits in Tg2576 mice.</a> Behav. Brain Res. 189, 126-138 (2008).</li><li>Deacon, R. M. J., Bannerman, D. M., Kirby, B. P., Croucher, A., Rawlins, J. N. P. <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+cytotoxic+hippocampal+lesions+in+mice+on+a+cognitive+test+battery.">Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery.</a> Behav. Brain Res. 133, 57-68 (2002).</li><li>Deacon, R. M. J., Rawlins, J. N. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Learning+impairments+of+hippocampal+lesioned+mice+in+a+paddling+pool.">Learning impairments of hippocampal lesioned mice in a paddling pool.</a> Behav. Neurosci. 116, 472-478 (2002).</li><li>Dellu, F., Mayo, W., Cherkoaoui, J., Le Moal, M., Simon, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+two-trial+memory+task+with+automated+recording:+study+in+young+and+aged+rats.">A two-trial memory task with automated recording: study in young and aged rats.</a> Brain Res. 558, 132-139 (1992).</li><li>Morris, R. G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatial+localization+does+not+require+the+presences+of+local+cues.">Spatial localization does not require the presences of local cues.</a> Learn. Motiv. 12, 239-260 (1981).</li><li>Russell, W. M. S., Burch, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The principles of humane experimental technique. , (1959).</li><li>Sanderson, D. J., Gray, A., Simon, A., Taylor, A. M., Deacon, R. M. J., Seeburg, P. H., Sprengel, R., Good, M. A., Rawlins, J. N. P., Bannerman, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deletion+of+glutamate+receptor-A+(GluR-A)+AMPA+receptor+subunits+impairs+one-trial+spatial+memory.">Deletion of glutamate receptor-A (GluR-A) AMPA receptor subunits impairs one-trial spatial memory.</a> Behav. Neurosci. 121, 559-569 (2007).</li><li>Sunyer, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Barnes+maze,+a+useful+task+to+assess+spatial+reference+memory+in+the+mice.">Barnes maze, a useful task to assess spatial reference memory in the mice.</a> Protocol Exchange. , (2007).</li><li>Wahlsten, D., Rustay, N. R., Metten, P., Crabbe, K. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+search+of+a+better+mouse+test.">In search of a better mouse test.</a> TINS. 26, 132-136 (2003).</li></ol>

没有利益冲突的声明。

总之，戏似乎是一个普遍有效的激励作用，避免了应力伴有深的水中游泳。不像在Morris水迷宫的路径长度和逃逸时间的措施，海马损伤的小鼠戏水池中的错误率保持不变，在整个训练期间5，所以这是一个纯粹的措施，而不是逃离时间或路径空间记忆长度，这既减少小鼠熟悉与非空间的元素的任务。错误措施受损（ 例如海马损毁）鼠和对照之间的差异也提供了一个更大的幅度。 在原来的出版物，探针测试进行检查，如果老鼠被真正使用空间线索5。探头1，迷宫旋转120°但转义管的地理位置仍然是在训练一样。表现大致维持不变。在探头2，类似的标准灭绝Morris水迷宫测试，退出管被阻塞。所花费的时间在训练中的迷宫，出口管位于象限，对照组为50％，25％的小鼠海马病变。在第三个探头测试中，出口管的位置改变，控制再花更多的时间在原来的培训象限。这些探头测试证实，小鼠没有使用intramaze线索，但在实验室迷宫外部空间线索指导。这种缺乏影响intramaze线索把巴恩斯迷宫优势的戏水池。 虽然我们还没有试过鼠戏迷宫，这是可能的，尽管它可能是一个优势，使水更冷，比20-25°C常使用在Morris水迷宫。然而，由于他们的身体不会被浸在水中，这应该不会有不利的福利效应。

莫里斯和巴恩斯迷宫由于实验心理学的开端，动物学习的研究倚重的迷宫，一般不透明的木材或金属构造。不可避免的，由于鼠类以非凡的嗅觉能力，使用他们的许多研究在一定程度上受到损害时，实验者认为他/她已经成功地在教学动物视觉或位置歧视，实际上已大鼠或小鼠主要使用嗅觉来解决这个问题。这集中体现大鼠海马病变是否可以进行空间参考记忆任务，详细论述了在2002年4争论。位于Olton大卫和同事，从本质上讲，从早期的工作与径向迷宫外，不出现总是有系统地旋转迷宫。这导致海马损伤的动物解决的任务，想必气味线索，将E独特的ACH臂。在牛津大学，（自然）曾一度盲目鼠标上观察到一个六臂迷宫。它离开其起始臂，并向右转。然后越过中心，并选择了相反的手臂。之后右转总是陷入千篇一律的策略，但是当它再次遇到已进入第一臂的基础，它把它的瞬间嗅出（约0.2​​秒），然后拒绝了，并移动到下臂。如果嗅觉信息可以记住一个单一的访问明确表示，它是一个静态的迷宫在反复试验测试，具有相同的手臂总是诱饵，会导致很强的嗅觉协会的奖励，并学习很容易会发生，即使病变阻止任何学习纯粹的空间。 这些问题，如刺激莫里斯发展自己的水迷宫，水不会提供恒定的局部嗅觉。 嬉水池本质上是一种混合传统之间周志武水迷宫设计的莫里斯7和干巴恩斯迷宫。在Morris水迷宫，在深水游泳的动物，这是逃脱浅水覆盖稍微淹没的平台，位于朝迷宫的中心。的Barnes迷宫，动物被放置在（干燥）的出口孔的周围的圆形平台，其中只有一个提供逃生置于下方的箱。 使用划桨作为逃生的动力源于问题报告不成比例时，一些转基因小鼠品系未能正确Morris水迷宫游泳。他们要么跌或被动地漂浮11。由于这可能代表了与压力有关的响应，它的理由是，减少了水戏深度足以克服这个问题，这的确有这样做。会议还决定，允许逃生的干管设置在一旁的仪器，而非浅水覆盖的平台。这将是一个更“自然”的逃避反应，增加了空间的组成部分的测试中，Morris水迷宫中的最初的学习是因为很多程序，动物首先必须克服其与生俱来的倾向一起游泳的迷宫的墙壁前空间学习就可以开始。 巴恩斯迷宫也可以承受从动物没有足够的动力逃跑的圆形平台10,11。

shallow water (paddling) variants of water maze tests in mice

当理查德·莫里斯于1981年7设计他的水迷宫，大部分工作是在大鼠行为。然而，小鼠遗传学的更深入的了解导致鼠标，变得越来越重要。但研究人员发现，一些菌株突变小鼠容易出现的问题，像被动浮动或潜水时，他们进行了测试Morris水迷宫11。这并不奇怪，考虑到它们的自然栖息地;，大鼠游泳自然（古典，“下水道老鼠”），而在干燥的中亚地区的演变小鼠。 为了克服这些问题，有人认为，浅水是否将提供足够的刺激对小鼠的逃逸动机。这也将避免干燥的小生灵，用毛巾，然后把它们放在温水复苏室，避免低温，这是一个更严重的问题，而不是老鼠的问题，鼠标的体积大的比表面积，使它p关节易受快速热损失。 另一个要考虑的是一个更自然的逃生策略是否可以使用，以方便学习。由于动物落入水中，游泳，远离岸边的安全是不可能传递他们的基因，动物进化出一种自然的倾向游到水体的边缘。 Morris水迷宫，但是，需要他们游到朝迷宫的中心 - 一个隐藏的平台正好相反，他们进化的行为。因此，嬉水迷宫应纳入逃生设备的边缘。此功能，加上与相对非厌恶浅水使用，体现“雅”方面的“3 RS”罗素和伯奇8。 不同类型的迷宫设计试图共同的特点是，水总是浅（深2厘米）和逃生是通过一根管子刺入设备的透明墙。其他管（“假出口“）也放在周围的墙壁，但这些被封锁的迷宫从里面全是假的退出和单真正的退出看起来相同。目前十二次（12面）迷宫是在使用牛津，12真/假退出设置在角落。透明划桨Y-迷宫在最近的发展已经测试成功。

<html>海马病变大大削弱学习的嬉水池5。使用一个戏Y-迷宫，年龄依赖性的赤字已经被证明在10和14，但不是3月龄Tg2576小鼠（淀粉样蛋白过度表达）的模型。老年（21个月）对照组小鼠也表现不佳3。一个空间的新奇内存运行在干燥的Y-迷宫实验发现敲除小鼠的谷氨酸受体-A（GLUR-A）AMPA受体亚基9障碍。 <img alt="图1" src="/files/ftp_upload/2608/2608fig1.jpg" /> 图1。鼠标MK 1在圆形嬉水池。 <img alt="图2" src="/files/ftp_upload/2608/2608fig2.jpg" /> 图2。鼠标发现嬉水池的出口管。 图3“SRC =”/ files/ftp_upload/2608/2608fig3.jpg“/&gt; 图3。鼠标逸入出口管。然后，该管脱离迷宫和鼠标返回到其家笼。 <img alt="图4" src="/files/ftp_upload/2608/2608fig4.jpg" /> 图4。鼠标在十二次的嬉水池。 <img alt="图5" src="/files/ftp_upload/2608/2608fig5.jpg" /> 图5鼠标犯的一个错误，因为它接近一个虚假的出口。 <img alt="图6" src="/files/ftp_upload/2608/2608fig6.jpg" /> 图6。错误致力于鼠标的鼻子内自带一个头的距离虚假出口。真正的退出是其右，出口管连接。 图7。嬉水Y-迷宫。 <img alt="图8" src="/files/ftp_upload/2608/2608fig8.jpg" /> 图8的出口的详细的臂端部的Y-迷宫。一个浅U形槽毗邻退出在端壁孔。这支持了出口管，下方支撑在上面的图片所示。出口管可以拆下回其家乡笼拿鼠标的支持。所有武器都配有这套了，但只有一只手臂端壁有一个圆形孔切成允许逃生。 <img alt="图9" src="/files/ftp_upload/2608/2608fig9.jpg" /> 图9：鼠标在一个死胡同划桨的Y-迷宫。 <img alt="图10" srC =“/ files/ftp_upload/2608/2608fig10.jpg”/&gt; 图10。鼠标找到的出口管。 <img alt="图11" src="/files/ftp_upload/2608/2608fig11.jpg" /> 图11。逃离划桨的Y-迷宫，等待鼠标，返回到其家笼。 <img alt="图12" src="/files/ftp_upload/2608/2608fig12.jpg" /> 图12。小鼠一般都可以依靠，而他们留在管抬回附近的家笼。 <img alt="图13" src="/files/ftp_upload/2608/2608fig13.jpg" /> 图13。Y-迷宫空间新奇配置结合一个嬉水Y-迷宫。一个不透明的闸门在一个臂的近端插入到幻灯片，透明铡关闭出口孔的门封条。

Watch this Scientific Journal Video about Shallow Water Paddling Variants of Water Maze Tests in Mice at JoVE.com

Shallow Water Paddling Variants of Water Maze Tests in Mice

小鼠<em&gt;可以</em&gt;游泳，但出现多株发现这个活动的压力。为了克服此问题已经设计出迷宫逃离浅水用来激励行为。这些已被证明支持学习至少作为良好的传统和广泛使用Morris水迷宫。

浅水（杖刑）的变体在小鼠体内的水迷宫测试

When Richard Morris devised his water maze in 19817, most behavioral work was done in rats. However, the greater understanding of mouse genetics led to ...

shallow-water-paddling-variants-of-water-maze-tests-in-mice

Research

JoVE Journal

Behavior

Shallow Water (Paddling) Variants of Water Maze Tests in Mice

23.2K 次观看.  University of Oxford. 小鼠可以游泳，但出现多株发现这个活动的压力。为了克服此问题已经设计出迷宫逃离浅水用来激励行为。这些已被证明支持学习至少作为良好的传统和广泛使用Morris水迷宫。

视频: Shallow Water Paddling Variants of Water Maze Tests in Mice

Use of an Eight-arm Radial Water Maze to Assess Working and Reference Memory Following Neonatal Brain Injury

Working and reference memory are commonly assessed using the land based radial arm maze.&#160;However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.

The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs.

Working and reference memory are commonly assessed using the land based radial arm maze.&#160;However, this paradigm requires pretraining, food ...

科研

行为学

Marble Burying and Nestlet Shredding as Tests of Repetitive, Compulsive-like Behaviors in Mice

Obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD) are serious and debilitating psychiatric conditions and each constitutes a significant public health concern, particularly in children. Both of these conditions are highlighted by the repeated expression of meaningless behaviors. Individuals with OCD often show checking, frequent hand washing, and counting. Children with ASDs also engage in repetitive tapping, arm or hand flapping, and rocking. These behaviors can vary widely in intensity and frequency of expression. More intense forms of repetitive behaviors can even result in injury (e.g.&#160;excessive grooming, hand washing, and self-stimulation). These behaviors are therefore very disruptive and make normal social discourse difficult. Treatment options for repetitive behaviors in OCD and ASDs are somewhat limited and there is great interest in developing more effective therapies for each condition. Numerous animal models for evaluating compulsive-like behaviors have been developed over the past three decades. Perhaps the animal models with the greatest validity and ease of use are the marble burying test and the nestlet shredding test. Both tests take advantage of the fact that the target behaviors occur spontaneously in mice. In the marble burying test, 20 marbles are arrayed on the surface of clean bedding. The number of marbles buried in a 30 min session is scored by investigators blind to the treatment or status of the subjects. In the nestlet shredding test, a nestlet comprised of pulped cotton fiber is preweighed and placed on top of cage bedding and the amount of the nestlet remaining intact after a 30 min test session is determined. Presently, we describe protocols for and show movie documentation of marble burying and nestlet shredding. Both tests are easily and accurately scored and each is sensitive to small changes in the expression of compulsive-like behaviors that result from genetic manipulations, disease, or head injury.

Disease, head injury, genetic modifications, and treatment of mice with drugs can have profound effects on behavior. Utilizing well-characterized and validated approaches such as marble burying and nestlet shredding, compulsive-like behaviors can be documented accurately in mice as models of human obsessive-compulsive disorder and autism spectrum disorder.

Obsessive-compulsive disorder (OCD) and autism spectrum disorders (ASD) are serious and debilitating psychiatric conditions and each constitutes a ...

Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice

Animal models have proven to be invaluable to researchers trying to answer questions regarding the mechanisms of behavior. The Open Field Maze is one of the most commonly used platforms to measure behaviors in animal models. It is a fast and relatively easy test that provides a variety of behavioral information ranging from general ambulatory ability to data regarding the emotionality of the subject animal. As it relates to rodent models, the procedure allows the study of different strains of mice or rats both laboratory bred and wild-captured. The technique also readily lends itself to the investigation of different pharmacological compounds for anxiolytic or anxiogenic effects. Here, a protocol for use of the open field maze to describe mouse behaviors is detailed and a simple analysis of general locomotor ability and anxiety-related emotional behaviors between two strains of C57BL/6 mice is performed. Briefly, using the described protocol we show Wild Type mice exhibited significantly less anxiety related behaviors than did age-matched Knock Out mice while both strains exhibited similar ambulatory ability.

A protocol is provided to use an Open Field Maze to access general locomotor activity, anxiety and emotionality in a laboratory mouse model.

使用开放式现场迷宫来衡量小鼠的运动能力和焦虑样行为

Animal models have proven to be invaluable to researchers trying to answer questions regarding the mechanisms of behavior. The Open Field Maze is one of ...

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer&#8217;s disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer&#8217;s disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

This manuscript describes a Morris water maze (MWM) protocol tailored for use with a commonly used mouse model of Alzheimer's disease. The MWM is widely used in transgenic mouse models. Implementation of a procedure sensitive to the background strain of the mouse model is essential for detecting group differences.

Morris水迷宫实验：优化小鼠品系和测试环境

 The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, ...

Place and Response Learning in the Open-field Tower Maze

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for examining how rats learn to use a place- or response-learning to successfully navigate in an open-field arena. Additionally, this protocol describes how the OFTM differs from other behavioral maze paradigms that are commonly used to study spatial learning in rodents. The OFTM described in this article was adapted from the one previously described by Cole, Clipperton, and Walt (2007). Specifically, the OFTM was created to test spatial learning in rodents without the experimenter having to consider how &#8220;stress&#8221; might play a role as a confounding variable. Experiments have shown that stress-alone can significantly affect cognitive function1. The representative results section contains data from an experiment that used the OFTM to examine the effects of estradiol treatment on place- and response-learning in adult female Sprague Dawley rats2. Future studies will be designed to examine the role of the hippocampus and striatum in place- and response-learning in the OFTM.

The Open-field Tower Maze (OFTM) is a maze created to study the behavioral and neural mechanisms of spatial learning (e.g., place- or response-learning) in rats. This maze is especially useful for experimenters who want to use a non-stressful maze paradigm to investigate spatial learning in their research.

在打开场塔迷宫的地方，反应学习

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for ...

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

This protocol describes a novel and efficient method to quickly initiate operant responding for ethanol in rats that, contrary to standard methods, does not require water deprivation or saccharin/sucrose fading to initiate responding.

一种用于评价大鼠乙醇的补强性能没有禁水，糖精衰落或扩展访问训练方法

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods ...

A Protocol of Manual Tests to Measure Sensation and Pain in Humans

Numerous qualitative and quantitative techniques can be used to test sensory nerves and pain in both research and clinical settings. The current study demonstrates a quantitative sensory testing protocol using techniques to measure tactile sensation and pain threshold for pressure and heat using portable and easily accessed equipment. These techniques and equipment are ideal for new laboratories and clinics where cost is a concern or a limiting factor. We demonstrate measurement techniques for the following: cutaneous mechanical sensitivity on the arms and legs (von-Frey filaments), radiant and contact heat sensitivity (with both threshold and qualitative assessments using the Visual Analog Scale (VAS)), and mechanical pressure sensitivity (algometer, with both threshold and the VAS). The techniques and equipment described and demonstrated here can be easily purchased, stored, and transported by most clinics and research laboratories around the world. A limitation of this approach is a lack of automation or computer control. Thus, these processes can be more labor intensive in terms of personnel training and data recording than the more sophisticated equipment. We provide a set of reliability data for the demonstrated techniques. From our description, a new laboratory should be able to set up and run these tests and to develop their own internal reliability data.

The goal of this procedure is to demonstrate a battery of quantitative techniques for sensory and pain measurement in humans. The equipment and techniques described are commonly found in pain clinics or are easy to obtain.

手动测试的协议来衡量感觉和疼痛人类

Numerous qualitative and quantitative techniques can be used to test sensory nerves and pain in both research and clinical settings. The current study ...

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 ...

Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and validated for rat use. The Radial Water Tread (RWT) maze test of spatial memory (designed specifically for mice and requiring no swimming) has been shown previously to successfully distinguish between controlled cortical impact-induced TBI mice and sham controls. Here, a detailed protocol for this task is presented. The RWT maze capitalizes on the natural tendency of mice to avoid open areas in favor of hugging the sides of an apparatus (thigmotaxis). The walls of the maze are lined with nine escape holes placed above the floor of the apparatus, and mice are trained to use visual cues to locate the escape hole that leads out of the maze. The maze is filled with an inch of cold water, sufficient to motivate escape but not deep enough to require that the mouse swim. The acquisition period takes only four training days, with a test of memory retention on day five and a long-term memory test on day 12. The results reported here suggest that the RWT maze is a feasible alternative to rat-validated, swimming-based cognitive tests in the assessment of spatial memory deficits in mouse models of TBI.

Here we present a protocol for a mouse-specific test of cognition that does not require swimming. This test can be used to successfully distinguish controlled cortical impact-induced traumatic brain injury mice from sham controls.

使用径向水痕迷宫评估外伤性脑损伤小鼠模型中的空间记忆障碍

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and ...

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. ...