这项工作是由加拿大卫生研究院研究院（CIHR），汤森家庭，和杰克布朗和家庭阿尔茨海默氏症研究基金会（到WAS）的支持。 WAS是加拿大研究主席在阿尔茨海默氏病的人。 PL是一个NSERC亚历山大格雷厄姆贝尔加拿大研究生奖学金博士后科研奖和迈克尔史密斯健康研究基金会高级研究生助学金的支持。

1。制备<ol><li>设备的准备工作<ol><li>获取与150厘米直径和深度为50cm（图1）的圆形水池。如果使用的是黑色的老鼠，白池应使用;如果使用的是白老鼠，应使用黑色池。 </li><li>安排的房间，被测试的动物无法看到在测试过程中，实验者。这可以用窗帘或房间隔断。 </li><li>在房间里放置的高对比度空间感，和/或对室内游泳池的位置，这将高出水面。 </li><li>将在游泳池直径10cm平台 - 白色为白池，清晰的黑色池有机玻璃。装满水的池中，直到平台高出水面1厘米。让水平衡至室温（22℃）。根据水的温度，这可能需要一至三天，或者可以加入热水，加快了平衡。 </li></ol></li><li>软件的编制<ol><li>在计算机软件的校准池，使相机可以创建从基于像素的信息物理距离信息。分成4个象限池。指定作为一个变量可以改变每次试验区的平台区。创建5个平台子区域 - 在每个象限，并在池的中心之一。保存校准和使用，其余的测试天。 （例如图2）。 </li><li>设置最大试验时间为60秒。如果鼠标的平台，在此之前找到程序的软件平台被发现时停止试验。 </li><li>指定程序开始自动跟踪，当实验者退出试验区。利用任何“反射最小化”选项，你的软件包提供。 </li><li>跟踪路径的长度，逃避潜伏期和时间花费在每个象限。 </li></ol></li></ol> 2。第1天：可视化平台<ol><li>计算机程序<ol><li>跟踪软件装入池校准。 </li><li>创建5个试验，审间的间隔，适合你的实验。编程平台的位置，并开始每次试验不同的方向。请参阅表1为例协议。 </li></ol></li><li>测试过程<ol><li>将小鼠从他们的住房设施的行为房间。保持在一个地区，在那里他们可以没有看到游泳池或空间线索的老鼠。让他们适应新的环境测试前至少30分钟。 </li><li>放置在平台上，以提高其知名度的一个标志。 </li><li>要开始测试，电梯从家里笼鼠标尾部的基础。支持鼠标，你把它的试验区。解除鼠标的尾巴基地，轻轻放入水中鼠标，面向池边。迅速离开试验区。 </li><li>如果鼠标发现截止前60秒的平台，让鼠标的平台上停留5秒钟，然后返回到其家笼。如果鼠标没有找到平台，平台上放置鼠标和允许留20秒，然后返回到其家笼。 </li><li>重复线索小鼠。随后的审讯开始每个不同的平台的位置和方向开始，你已经到你的软件编程。 </li><li>当测试完成后，返回的老鼠，他们的住房设施。小鼠干之前返回到动物设施的正常体温是保证。 </li><li>在翌日准备，从平台中删除的国旗和添加额外的水淹没的平台，在地表以下1厘米池。 </li></ol></li></ol> 3。 2-5：隐藏的平台<ol><li>计算机程序<ol><li>跟踪软件装入池校准。 </li><li>创建5个试验，审间的间隔，适合你的实验。计划的平台位置保持在相同的位置在所有试验和天，但出发方向不同，每次试验中，每一天。 </li></ol></li><li>测试过程<ol><li>黑鼠，无毒，白色粉末温度油漆添加到池中，调匀。使用足够的涂料等，被淹没的平台是从水面不可见。对于白老鼠，与清澈的海水和明确的有机玻璃平台的黑色游泳池应该使用。 </li><li>按照步骤2.2.3至2.2.6。 </li></ol></li></ol> 4。第6天：探头审判<ol><li>计算机程序<ol><li>跟踪软件装入池校准。 </li><li>创建1审判没有平台区，和一开始的方向。从2-5天使用的平台象限最远的起始方向是首选。径长度为60秒。 </li></ol></li><li>测试过程<ol><li>从池中删除的平台。 </li><li>按照步骤2.2.3至2.2.6。 </li></ol></li></ol> 5。数据分析<ol><li>对于每一天，每一个鼠标，平均5个试验，每个测试题目给一个单一的路径长度和逃避潜伏期。正确计算相结合的错误。对于第6天，只需收集路径的长度，逃避潜伏期和时间花费在每个鼠标的平台象限。 </li><li>如果组第1天之间存在的任何分歧，它可能是一个问题，而不是学习和记忆的视野。只有1天进行分析，如果没有差异。 </li><li>比较天使用适合您的数据集的统计数据2-5的学习曲线。一个陡峭的曲线代表更快的任务收购;浅的曲线表示在收购任务的赤字。从2天到5天的数据分析使用ANOWA。 </li><li>第6天，比较％的时间花费在以前学过的平台象限，使用适合你的数据集的统计数据。一个较高的百分比在平台象限所花费的时间将被解释为一个更高级别的内存保留。 </li></ol> 6。代表性的成果我们用Morris水迷宫测试，以检查AD的发病机制（7）和丙戊酸（VPA）的转基因AD模型小鼠的治疗AD（6）医药潜力缺氧的效果。图3是代表性的结果，我们在我们丙戊酸钠的记忆障碍的影响，在APP23 AD小鼠模型（6）研究报告。在第1天（可视化平台试验），没有VPA治疗组和对照组（图3A）在延迟和路径长度（图3A），表明这两个组也有类似的电机和可视化功能之间的差异。我们从这个假设的老鼠能够看到标记的平台和周围环境的线索，可以游泳，可以接受的。 2-5天（隐藏的平台试验的第1天至4）的例子显示了一个在逃避潜伏期（图3C），组与组之间的路径长度（图3D）的区别，表明丙戊酸钠治疗小鼠的表现明显比对照组更好随着时间的推移。探头线索的最后一天（6日）显示结果，多次前往小鼠进入第三象限，是以前被隐藏的平台，与丙戊酸钠治疗控制（图3E）相比显着。这些数据表明，丙戊酸钠治疗显着提高APP23小鼠的记忆中看到的赤字。 <img src="/files/ftp_upload/2920/2920fig1.jpg" alt="图1"/> 图1。 Morris水迷宫可见平台测试当天的设备安装 。池屏蔽从实验者使用房间隔断。位于空间线索的墙壁上，可能放置在室内池，水面以上，如果需要的话。池充满了清澈的水，表面上方1厘米平台。一个标志，一直放在提升知名度的平台。 <img src="/files/ftp_upload/2920/2920fig2.jpg" alt="图2"/> 图2。屏幕捕获的任何迷宫™视频跟踪，展示池校准系统 。池是从上面看，一个RTV24数字转换器的模拟跟踪摄像机由黑色和白色。几个区域内的软件定义和划分成4个象限的总池。第五，平台区的输入可以各不相同试验的5个可能的地点：西北，东北，西南，东南，或者中心。添加一个校准线（打勾跨越中心线），让软件将其转换成物理距离的像素距离。 <img src="/files/ftp_upload/2920/2920fig3.jpg" alt="图3"/> 图3。 Morris水迷宫代表性的结果。，7个月APP23携带人类瑞典突变APP基因的转基因小鼠每天VPA（N = 30只小鼠）或车辆溶液（N = 30只小鼠）注射一个月后进行了测试。（a ）在的可视化平台测试的第一天，丙戊酸钠治疗和控制APP23小鼠表现出类似的延迟逃脱的可视化平台上。 （二）P &lt;0.05学生的t检验。VPA的治疗和控制APP23小鼠收到类似的游泳距离在可视化平台测试的可视化平台上逃跑。 P&gt; 0.05由学生的t检验。隐藏的平台测试，丙戊酸钠治疗APP23小鼠一个较短的延迟，以逃脱的3 号和第 4天，P到的隐藏平台&lt;由方差0.001。（四）丙戊酸钠治疗APP23小鼠面前逃避到隐藏平台上的第3 次和第 4天，P &lt;0.01由方差一个游泳的长度较短（E）在第6天的探测试验，丙戊酸钠治疗APP23小鼠前往进入第三象限，是以前被隐藏的平台，更多的时间比对照组显着。 * P &lt;0.005学生的t检验。 （改编并从205医学实验 ，2781年至2789年，2008年，美国洛克菲勒大学出版社出版的医学期刊在J.进出口， 杂志转载。10.1084/jem.20081588）（6）。 <table border="1"><tbody><tr><td>&nbsp;</td><td colspan="2"> 第1天 </td><td> 第2天 </td><td> 第3天 </td><td> 第4天 </td><td> 第5天 </td><td> 第6天 </td></tr><tr><td></td><td> 平台的位置 </td><td> 起始方向 </td><td colspan="4"> 平台位置：西南启动位置如下： </td><td> 没有平台。 </td></tr><tr><td> 审判1 </td><td>申银万国</td><td>小号</td><td> W </td><td> ñ </td><td> ñ </td><td> Ë </td><td> ñ </td></tr><tr><td> 审判2 </td><td>净重</td><td> ñ </td><td>小号</td><td> W </td><td> Ë </td><td>小号</td><td></td></tr><tr><td> 试用3 </td><td>东北</td><td>小号</td><td> ñ </td><td> Ë </td><td> W </td><td> W </td><td></td></tr><tr><td> 审判4 </td><td>中心</td><td> Ë </td><td> Ë </td><td> W </td><td>小号</td><td> Ë </td><td></td></tr><tr><td> 试验5 </td><td>东南</td><td> W </td><td>小号</td><td>小号</td><td> ñ </td><td> ñ </td><td></td></tr></tbody></table> 表1。样品水迷宫协议* *请注意平台的位置，第1天开始改变方向，而2-5天的平台的地位保持不变，而出发的方向变化。第6天，有没有平台和审单。第6天开始的方向是最远从以前的平台位置（SW），使小鼠必须旅行之前进入以前学过的平台象限的一段距离。

<ol><li>Morris, R. G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Spatial+localization+does+not+require+the+presence+of+local+cues%5BTitle%5D)+AND+%22Learning+and+Motivation%22%5BJournal%5D)">Spatial localization does not require the presence of local cues.</a> Learning and Motivation. 12, 239-260 (1981).</li>
<li>O'Keefe, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+review+of+the+hippocampal+place+cells%5BTitle%5D)+AND+%22Prog+Neurobiol%22%5BJournal%5D)">A review of the hippocampal place cells.</a> Prog Neurobiol. 13, 419-439 (1979).</li>
<li>Scoville, W. B., Milner, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Loss+of+recent+memory+after+bilateral+hippocampal+lesions%5BTitle%5D)+AND+%22J+Neurol+Neurosurg+Psychiatry%22%5BJournal%5D)">Loss of recent memory after bilateral hippocampal lesions.</a> J Neurol Neurosurg Psychiatry. 20, 11-21 (1957).</li>
<li>Eichenbaum, H., Stewart, C., Morris, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Hippocampal+representation+in+place+learning%5BTitle%5D)+AND+%22J+Neurosci%22%5BJournal%5D)">Hippocampal representation in place learning.</a> J Neurosci. 10, 3531-3542 (1990).</li>
<li>Block, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Global+ischemia+and+behavioural+deficits%5BTitle%5D)+AND+%22Progress+in+Neurobiology%22%5BJournal%5D)">Global ischemia and behavioural deficits.</a> Progress in Neurobiology. 58, 279-295 (1999).</li>
<li>Qing, H., He, G., Ly, P. T., Fox, C. J., Staufenbiel, M., Cai, F., Zhang, Z., Wei, S., Sun, X., Chen, C. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Valproic+acid+inhibits+Abeta+production%2C+neuritic+plaque+formation%2C+and+behavioral+deficits+in+Alzheimer%27s+disease+mouse+models%5BTitle%5D)+AND+%22J+Exp+Med%22%5BJournal%5D)">Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models.</a> J Exp Med. 205, 2781-2789 (2008).</li>
<li>Sun, X., He, G., Qing, H., Zhou, W., Dobie, F., Cai, F., Staufenbiel, M., Huang, L. E., Song, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Hypoxia+facilitates+Alzheimer%27s+disease+pathogenesis+by+up-regulating+BACE1+gene+expression%5BTitle%5D)+AND+%22Proc+Natl+Acad+Sci+U+S+A%22%5BJournal%5D)">Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression.</a> Proc Natl Acad Sci U S A. , 18727-18732 (2006).</li>
<li>D'Hooge, R., De Deyn, P. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Applications+of+the+Morris+water+maze+in+the+study+of+learning+and+memory%5BTitle%5D)+AND+%22Brain+Research+Reviews%22%5BJournal%5D)">Applications of the Morris water maze in the study of learning and memory.</a> Brain Research Reviews. 36, 60-90 (2001).</li>
<li>Brandeis, R., Brandys, Y., Yehuda, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+use+of+the+Morris+Water+Maze+in+the+study+of+memory+and+learning%5BTitle%5D)+AND+%22Int+J+Neurosci%22%5BJournal%5D)">The use of the Morris Water Maze in the study of memory and learning.</a> Int J Neurosci. 48, 29-69 (1989).</li>
<li>Lipp, H. P., Wolfer, D. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Genetically+modified+mice+and+cognition%5BTitle%5D)+AND+%22Curr+Opin+Neurobiol%22%5BJournal%5D)">Genetically modified mice and cognition.</a> Curr Opin Neurobiol. 8, 272-280 (1998).</li>
<li>Sandi, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+role+and+mechanisms+of+action+of+glucocorticoid+involvement+in+memory+storage%5BTitle%5D)+AND+%22Neural+Plast%22%5BJournal%5D)">The role and mechanisms of action of glucocorticoid involvement in memory storage.</a> Neural Plast. 6, 41-52 (1998).</li>
</ol>

所有实验均在与不列颠哥伦比亚省的动物护理和使用委员会和CIHR指引大学的规定进行。

年龄，性别，品种，和应变的差异影响的MWM性能（8）。研究表明，老年小鼠在MWM表现不佳，而男性的啮齿类动物的表现比女性更好;此外，浮动比老鼠（9，10）的小鼠更明显。因此，这些元素应等同于在所有的测试。证据还表明，强调动物的MWM（11）执行更差，因此环境因素可能会造成压力，如温度，光照和噪音，，应监测和保持常数了任务。

<table border="1"><tbody><tr><th>试剂名称</th><th>公司</th><th>评论（可选） </th></tr><tr><td> AnyMaze视频跟踪系统</td><td> Stoelting公司</td><td></td></tr><tr><td>彩画漆</td><td>里夫斯＆普尔组</td><td>白，粉</td></tr></tbody></table>

morris water maze test for learning and memory deficits in alzheimer&#39;s disease model mice

神经学家理查德G.莫里斯Morris水迷宫（MWM）最初成立于1981年，以测试海马依赖的学习，包括收购空间memoryand长期空间记忆 1 。 MWM的是一个相对简单的的程序通常包含进行为期6天的试验中，之间的空间（隐藏平台的主要优势）的分化和非空间（可视化平台）的条件下 2-4 。此外，MWM的测试环境，减少气味径干扰 5 。这导致了广泛的任务要使用的空间学习和记忆的神经生物学和神经药理学的研究。的MWM中起着重要作用，在啮齿类动物模型的神经认知障碍，如阿尔茨海默氏病6，7验证。在这个协议中，我们讨论的MWM测试学习记忆和阿尔茨海默氏症的转基因小鼠模型中常用的数据分析的典型过程。

Watch this Scientific Journal Video about Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice at JoVE.com

Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice

Morris水迷宫测试海马依赖的学习和记忆是一种行为的任务。它已被广泛应用在神经生物学，神经和神经紊乱的啮齿动物模型的研究。

在阿尔茨海默氏病模型小鼠学习和记忆障碍的Morris水迷宫测试

The Morris Water Maze (MWM) was first established by neuroscientist Richard G. Morris in 1981 in order to test hippocampal-dependent learning, including ...

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Neuroscience

Morris Water Maze Test for Learning and Memory Deficits in Alzheimer&#39;s Disease Model Mice

127.3K 次观看.  University of British Columbia. Morris水迷宫测试海马依赖的学习和记忆是一种行为的任务。它已被广泛应用在神经生物学，神经和神经紊乱的啮齿动物模型的研究。

视频: Morris Water Maze Test for Learning and Memory Deficits in Alzheimer's Disease Model Mice

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

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 the mouse becoming increasingly important. But researchers found that some strains of mutant mice were prone to problems like passively floating or diving when they were tested in the Morris water maze11. This was unsurprising considering their natural habitat; rats swim naturally (classically, the "sewer rat"), whereas mice evolved in the dry areas of central Asia.
To overcome these problems, it was considered whether shallow water would be a sufficient stimulus to provide escape motivation for mice. This would also avoid the problems of drying the small creatures with a towel and then putting them in a heated recovery chamber to avoid hypothermia, which is a much more serious problem than with rats; the large ratio of surface area to volume of a mouse makes it particularly vulnerable to rapid heat loss.
Another consideration was whether a more natural escape strategy could be used, to facilitate learning. Since animals that fall into water and swim away from the safety of the shore are unlikely to pass on their genes, animals have evolved a natural tendency to swim to the edge of a body of water. The Morris water maze, however, requires them to swim to a hidden platform towards the center of the maze - exactly opposite to their evolved behavior. Therefore the paddling maze should incorporate escape to the edge of the apparatus. This feature, coupled with the use of relatively non-aversive shallow water, embodies the "Refinement" aspect of the "3 Rs" of Russell and Burch8.
Various types of maze design were tried; the common feature was that the water was always shallow (2 cm deep) and escape was via a tube piercing the transparent wall of the apparatus. Other tubes ("false exits") were also placed around the walls but these were blocked off. From the inside of the maze all false exits and the single true exit looked the same. Currently a dodecagonal (12-sided) maze is in use in Oxford, with 12 true/false exits set in the corners. In a recent development a transparent paddling Y-maze has been tested successfully.

Shallow Water Paddling Variants of Water Maze Tests in Mice

Mice can swim, but many strains appear to find this activity stressful. To overcome this problem mazes have been devised where escape from shallow water is used to motivate behaviour. These have been demonstrated to support learning at least as good as the traditional and widely used Morris water maze.

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 ...

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行为学

Low-stress Route Learning Using the Lashley III Maze in Mice

Many behavior tests designed to assess learning and memory in rodents, particularly mice, rely on visual cues, food and/or water deprivation, or other aversive stimuli to motivate task acquisition. As animals age, sensory modalities deteriorate. For example, many strains of mice develop hearing deficits or cataracts. Changes in the sensory systems required to guide mice during task acquisition present potential confounds in interpreting learning changes in aging animals. Moreover, the use of aversive stimuli to motivate animals to learn tasks is potentially confounding when comparing mice with differential sensitivities to stress. To minimize these types of confounding effects, we have implemented a modified version of the Lashley III maze. This maze relies on route learning, whereby mice learn to navigate a maze via repeated exposure under low stress conditions, e.g. dark phase, no food/water deprivation, until they navigate a path from the start location to a pseudo-home cage with 0 or 1 error(s) on two consecutive trials. We classify this as a low-stress behavior test because it does not rely on aversive stimuli to encourage exploration of the maze and learning of the task. The apparatus consists of a modular start box, a 4-arm maze body, and a goal box. At the end of the goal box is a pseudo-home cage that contains bedding similar to that found in the animal&#x2019;s home cage and is specific to each animal for the duration of maze testing. It has been demonstrated previously that this pseudo-home cage provides sufficient reward to motivate mice to learn to navigate the maze1. Here, we present the visualization of the Lashley III maze procedure in the context of evaluating age-related differences in learning and memory in mice along with a comparison of learning behavior in two different background strains of mice. We hope that other investigators interested in evaluating the effects of aging or stress vulnerability in mice will consider this maze an attractive alternative to behavioral tests that involve more stressful learning tasks and/or visual cues.

The Lashley III maze is a route-learning task that does not rely on aversive stimuli or visual cues. It is thus a highly attractive option for evaluating learning and memory, especially in aging mice or otherwise where stress is a consideration.

低应力路线学习，在老鼠身上使用拉什利三迷宫

Many behavior tests designed to assess learning and memory in rodents, particularly mice, rely on visual cues, food and/or water deprivation, or other ...

神经科学

Quantifying Cognitive Decrements Caused by Cranial Radiotherapy

With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For many patients afflicted with CNS and non-CNS malignancies, radiotherapy and chemotherapy offer the best options for disease control. These treatments however come at a cost, and nearly all cancer survivors (~11 million in the US alone as of 2006) incur some risk for developing cognitive dysfunction, with the most severe cases found in patients subjected to cranial radiotherapy (~200,000/yr) for the control of primary and metastatic brain tumors1. Particularly problematic are pediatric cases, whose long-term survival plagued with marked cognitive decrements results in significant socioeconomic burdens2. To date, there are still no satisfactory solutions to this significant clinical problem.
We have addressed this serious health concern using transplanted stem cells to combat radiation-induced cognitive decline in athymic rats subjected to cranial irradiation3. Details of the stereotaxic irradiation and the in vitro culturing and transplantation of human neural stem cells (hNSCs) can be found in our companion paper (Acharya et al., JoVE reference). Following irradiation and transplantation surgery, rats are then assessed for changes in cognition, grafted cell survival and expression of differentiation-specific markers 1 and 4-months after irradiation. To critically evaluate the success or failure of any potential intervention designed to ameliorate radiation-induced cognitive sequelae, a rigorous series of quantitative cognitive tasks must be performed. To accomplish this, we subject our animals to a suite of cognitive testing paradigms including novel place recognition, water maze, elevated plus maze and fear conditioning, in order to quantify hippocampal and non-hippocampal learning and memory. We have demonstrated the utility of these tests for quantifying specific types of cognitive decrements in irradiated animals, and used them to show that animals engrafted with hNSCs exhibit significant improvements in cognitive function3.
The cognitive benefits derived from engrafted human stem cells suggest that similar strategies may one day provide much needed clinical recourse to cancer survivors suffering from impaired cognition. Accordingly, we have provided written and visual documentation of the critical steps used in our cognitive testing paradigms to facilitate the translation of our promising results into the clinic.

Cognitive impairment resulting from the radiotherapeutic management of brain tumors represents a clinically intractable condition that adversely impacts quality of life. The capability to critically evaluate potential interventions for ameliorating radiation-induced cognitive decrements ultimately depends on the capability to undertake rigorous quantitative assessments of cognition.

量化颅放疗引起的认知递减

With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For ...

医学

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, ...

Morris Water Maze Experiment

The Morris water maze is widely used to study spatial memory and learning. Animals are placed in a pool of water that is colored opaque with powdered non-fat milk or non-toxic tempera paint, where they must swim to a hidden escape platform. Because they are in opaque water, the animals cannot see the platform, and cannot rely on scent to find the escape route. Instead, they must rely on external/extra-maze cues. As the animals become more familiar with the task, they are able to find the platform more quickly. Developed by Richard G. Morris in 1984, this paradigm has become one of the "gold standards" of behavioral neuroscience.

The Morris water maze is a well-accepted tool used to document the involvement of the hippocampus in a behavioral task.

Morris水迷宫实验

The Morris water maze is widely used to study spatial memory and learning. Animals are placed in a pool of water that is colored opaque with powdered ...

生物学

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 ...

Analysis of Learning and Memory Ability in an Alzheimer's Disease Mouse Model using the Morris Water Maze

A Morris water maze (MWM) experiment forces experimental animals to swim and learn to find a platform hidden in the water. It is widely used in scientific research to assess the learning and memory of animals. Due to the extensive use of the MWM test, visual experimental protocols are essential for researchers. This manuscript uses the latest studies to introduce the protocol of the MWM test. Alzheimer&#8217; Disease (AD) is characterized by a progressive loss of memory and cognitive function. An alternative and complementary treatment used for AD is Manual Acupuncture (MA). To assess the learning and memory ability of AD model mice, the MWM test was conducted. The visible platform trial, hidden platform trial, probe trial, and reversal trial of MWM were used to evaluate spatial learning and memory ability. In the visible platform trial, the swimming speed and escape latency of mice in different groups was not significantly different. In the hidden platform and reversal trials, the AD group showed a long escape latency. The escape latency decreased significantly after the MA treatment. Low platform crossover number and the proportion of time in the SW quadrant in the probe trial increased after the MA treatment (p &#60; 0.05 or p &#60; 0.01). The results of the MWM tests suggest that MA can effectively improve the spatial learning and memory abilities of AD model mice. Rigorous experimental operations provided assurance of the reliability of the results.

Herein, a protocol to conduct the Morris water maze tests to evaluate the ability of learning and memory of Alzheimer&#8217;s Disease model mice and to assess the effect of manual acupuncture for treating them is described.

使用莫里斯水迷宫对阿尔茨海默氏病小鼠模型学习和记忆能力的分析

A Morris water maze (MWM) experiment forces experimental animals to swim and learn to find a platform hidden in the water. It is widely used in scientific ...

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke.
For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.

To investigate the co-morbid Alzheimer&#39;s disease (AD) and stroke condition in a novel model, three behavior tasks are described that assess both motor control and cognitive behaviors. These tasks include the beam-walk task, cylinder task and Morris water maze.

汽车和海马依赖空间学习和记忆参考评估与中风阿尔茨海默氏病的转基因大鼠模型

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk ...

<meta charset="utf8"></head><body>用于小鼠血管认知障碍研究的针头模型

A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis

Vascular cognitive impairment and dementia (VCID) results from vascular brain injury. Given VCID&#39;s high incidence, which is expected to continue rising as the population ages, it is critical to establish a robust animal model for the disease. This paper presents a novel method of creating a mouse model of VCID that is based on asymmetric bilateral common carotid artery stenosis, which mimics human chronic cerebral hypoperfusion caused by carotid atherosclerosis.
Briefly, common carotid arteries (CCAs) are ligated to different gauge needles (32 G for the right CCA and 34 G for the left CCA) using 7-0 silk sutures followed by immediate needle removal. The remaining suture rings cause persistent blood flow reduction and long-term cognitive impairment associated with white matter injury, microinfarcts, and reactive gliosis, thus closely mimicking the pathogenesis of VCID. Importantly, in this needle model, the clinical representations do not revert with time, providing reliable long-term cognitive impairment. Moreover, the survival rate 24 weeks post surgery was 81.6%, which is higher compared to the other established models of VCID with a similar level of blood flow reduction.
Additional advantages include low material cost and compatibility with MRI to monitor brain injury in live animals since no metal is implanted. The main challenge in employing the needle model of VCID is the requirement for developing advanced surgical skills since mouse CCAs are less than 0.6 mm in diameter and are very fragile. High-quality visual representation of the surgery will thus help researchers to master this technique and advance our understanding of VCID, potentially leading to the development of novel therapeutic modalities to decrease the devastating cognitive decline associated with VCID.

<meta charset="utf8"></head><body>基于针引导不对称双侧颈总动脉狭窄的血管性认知障碍和痴呆小鼠模型

The needle method of asymmetric bilateral common carotid artery stenosis is proposed to create a mouse model for vascular cognitive impairment and dementia. It results in longer-term outcomes compared to previously established models and is compatible with live MRI. Visual representation demonstrating the procedure provides guidance for mastering the surgery.

基于针引导不对称双侧颈总动脉狭窄的血管性认知障碍和痴呆小鼠模型

Vascular cognitive impairment and dementia (VCID) results from vascular brain injury. Given VCID&#39;s high incidence, which is expected to continue ...

在阿尔茨海默氏病模型小鼠学习和记忆障碍的Morris水迷宫测试

摘要

探索更多视频

浅水（杖刑）的变体在小鼠体内的水迷宫测试

低应力路线学习，在老鼠身上使用拉什利三迷宫

量化颅放疗引起的认知递减

Morris水迷宫实验:优化小鼠品系和测试环境

Morris水迷宫实验

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

使用莫里斯水迷宫对阿尔茨海默氏病小鼠模型学习和记忆能力的分析

汽车和海马依赖空间学习和记忆参考评估与中风阿尔茨海默氏病的转基因大鼠模型

基于针引导不对称双侧颈总动脉狭窄的血管性认知障碍和痴呆小鼠模型

基于针引导不对称双侧颈总动脉狭窄的血管性认知障碍和痴呆小鼠模型