Name: assessing spatial memory impairment in a mouse model of traumatic brain injury using a radial water tread maze
Uploaded: 2017-07-17T14:00:00
Description: Watch this Scientific Journal Video about Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze at JoVE.com

该研究得到了翻译健康科学研究所试点项目授予机会（UL1TR000423），华盛顿人类发展与残疾中心大学和华盛顿大学动物行为核心与脑成像核心的支持。我们要感谢Warren Ladiges博士在制定和传播这里提出的原始径向水面踏步迷宫设计和协议方面的作用。我们也感谢Toby Cole对这个项目的协助。

所有程序和动物处理均按照国家卫生研究院和华盛顿大学动物护理与使用委员会颁布的动物护理指南进行。 手术<ol><li>在诱导盒中麻醉5％异氟烷的老鼠，直到无意识。通过降低呼吸频率和在趾部夹紧后不存在撤回反射来确认麻醉。 </li><li>在手术过程中，通过鼻锥保持2-2.5％的麻醉。在整个手术过程中监测呼吸频率，以确保鼠标无意识。 </li><li>将鼠标放在加热垫上，并使用?...

<ol>
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L., Lipp, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatial+Memory+and+Learning+in+Transgenic+Mice:+Fact+or+Artifact?.">Spatial Memory and Learning in Transgenic Mice: Fact or Artifact?.</a> Physiology. 13 (3), 118-123 (1998).</li><li>Koopmans, G., Blokland, A., Vannieuwenhuijzen, P., Prickaerts, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+spatial+learning+abilities+of+mice+in+a+new+circular+maze.">Assessment of spatial learning abilities of mice in a new circular maze.</a> Physiol Behav. 79 (4-5), 683-693 (2003).</li><li>Deacon, R., Rawlins, N. <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 (3), 472-478 (2002).</li><li>Pettan-Brewer, C., 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=A+novel+radial+water+tread+maze+tracks+age-related+cognitive+decline+in+mice.">A novel radial water tread maze tracks age-related cognitive decline in mice.</a> Pathobiol Aging Age Relat Dis. 3, 1-4 (2013).</li><li>Wiley, J., Pettan-Brewer, C., Ladiges, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phenylbutyric+acid+reduces+amyloid+plaques+and+rescues+cognitive+behavior+in+AD+transgenic+mice.">Phenylbutyric acid reduces amyloid plaques and rescues cognitive behavior in AD transgenic mice.</a> Aging Cell. 10 (3), 418-428 (2011).</li><li>Enns, L., 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=Disruption+of+Protein+Kinase+A+in+Mice+Enhances+Healthy+Aging.">Disruption of Protein Kinase A in Mice Enhances Healthy Aging.</a> PLoS ONE. 4 (6), (2009).</li><li>Ivonen, H., Nurminen, L., Harri, M., Tanila, H., Puolivali, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypothermia+in+mice+tested+in+Morris+water+maze.">Hypothermia in mice tested in Morris water maze.</a> Behav Brain Res. 141 (2), 207-213 (2003).</li><li>Shultz, S. 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这里介绍的RWT迷宫协议成功地区分了CCI诱导的TBI小鼠和假手术对照，代表了可行的，以鼠标为中心的替代MWM和Barnes圆形迷宫。而在这里报道的结果只会讲的使用在TBI小鼠模型中RWT迷宫，该设备已成功应用于老年人和转基因模型，其中应力诱导基于游泳测试导致违规使用MWM不切实际15,17国产，18，19。不?...

记忆障碍是由创伤性脑损伤（TBI）1，2名患者报告的最常见的症状之一。因此，准确识别和评估TBI动物模型中的类似记忆缺陷对于我们对这种状况及其管理的理解至关重要。在这里，我们提出了一个使用径向水胎（RWT）迷宫测试TBI鼠标模型中的空间记忆的协议。以前显示该装置可以评估受控皮层影响（CCI）诱导的TBI 3的小鼠模型中的认知缺陷，并且代表了大鼠验证的，基于游泳的认知测试的潜在替代方案。 转基因小鼠模型的日益多样化和可用性已经导致科研4使用小鼠大鼠上最近有所增加。尽管有这种转变，研究人员继续依靠行为最初为老鼠使用设计和验证的认知任务。目前用于评估在小鼠中的认知中最常见的测试，Morris水迷宫（MWM）和巴恩斯圆形迷宫，是专门设计，以利用大鼠5,6发现本能的行为。考虑到这两个物种4之间存在的遗传，神经行为和认知的差异，这是不足为奇的小鼠上这些任务7,8始终表现不佳。 测试能力方面的物种依赖性差异特别涉及基于游泳的认知测试，如MWM。虽然大鼠和小鼠是基于游泳认知任务9,10显着表现不佳精通游泳，研究人员已经确定了几个小鼠品系， </SUP&gt; 11，12，13。即使是在野生型动物，老鼠通常优于小鼠7,8。虽然这可以解释为空间记忆中的物种特异性差异，但使用干地迷宫的类似随访测试显示认知表现没有物种依赖性差异8 。与认知无关的一些因素可以解释这一发现，包括游泳能力或搜索策略中的物种依赖性差异。事实上，MWM中小鼠特异性搜索策略的因素分析表明，非空间因素（特别是Thigomotaxis和被动[ 即浮动]）可能在MWM表现中起到比空间学习更重要的作用14 。 在这里，我们展示了使用认知测试来设计来利用它小鼠的直觉行为，不需要游泳，测量CCI诱导的TBI小鼠模型中的空间记忆障碍。虽然RWT迷宫（ 图1 的A-B）被设想为在MWM和Barnes圆形迷宫的新颖混合型，它是专为采取的行为thigmotactic本能给小鼠15,16优势。该设备包括一个32英寸直径的镀锌钢桶，其中九个均匀分布的出口孔已经钻孔。孔位于浴缸底部的2-1 / 4英寸处，并且尺寸适合普通可用的1-1 / 2英寸ABS DWV SPG x SJ陷阱适配器。八个出口被外部盖住，并且用橡皮塞挡住1英寸的深度。第九个通过90°丙烯腈丁二烯苯乙烯（ABS）弯头连接到不透明的塑料盒上，测试后可以从中轻松取出鼠标。在一个过程中短暂采集期间，老鼠训练使用迷宫内的独特视觉线索找到这个逃生箱。在测试过程中，迷宫充满了一英寸冷水（12-14°C），足够的足够强大的逃逸能力，但不足以使鼠标游泳。 在RWT迷宫表示一种低成本，低维护的替代MWM，并已在老年和转基因小鼠15，17，18，19成功地使用，和CCI诱导的TBI 3的小鼠模型。这里概述的方案代表了一种测量空间记忆障碍的简单有效的方法，不需要进行伤前训练，可以轻松修改以适应研究实验室的特殊需要。

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assessing spatial memory impairment in a mouse model of traumatic brain injury using a radial water tread maze

尽管近来在科学研究中使用小鼠模型的增加，研究人员继续使用最初设计和验证大鼠使用的认知任务。以前已经显示了空间记忆的径向水胎（RWT）迷宫测试（专为小鼠而设计，不需要游泳），以成功区分受控的皮层撞击诱导的TBI小鼠和假手术对照。在这里，介绍了此任务的详细协议。 RWT迷宫利用小鼠自然倾向避免开放区域，有利于拥抱设备的两侧（thigmotaxis）。迷宫的墙壁上装有九个放置在设备地板上的逃生孔，老鼠训练使用视觉线索来定位引出迷宫的逃生孔。迷宫充满了一英寸的冷水，足以激发逃脱，但不够深，要求鼠标游泳。收购期仅需四次天，在第5天进行记忆保留测试，并在第12天进行长期记忆测试。这里报告的结果表明，RWT迷宫是评估空间中大鼠验证的，基于游泳的认知测试的可行替代方案TBI小鼠模型的记忆缺陷。

RWT迷宫（ 图1 ）用于研究随机分配接受受控皮质冲击诱导的TBI或假手术的小鼠中损伤依赖性空间记忆缺陷。使用电磁驱动的皮质冲击产生损伤，其具有3mm的凸尖，并且以下损伤参数：6m / s的冲击速度，1mm的穿透深度和200ms的接触时间。小鼠从手术后35天开始接受认知测试，并进行了四天的培训（收购期），然后在第5天进行记忆保留测试，并在第12天?...

Watch this Scientific Journal Video about Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze at JoVE.com

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

在这里，我们提出了一个不需要游泳的认知的小鼠特异性测试方案。该测试可用于成功地区分受控皮质冲击引起的创伤性脑损伤小鼠与假手术对照。

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 ...

The overall goal of this Radial Water Tread Maze protocol is to test spatial memory in a mouse model of traumatic brain injury using a mouse centric cognitive task that does not require swimming. This method can be especially useful for testing cognition in mouse models, where motor deficits and or a lack of motivation makes swimming based cognitive testing protocols such as the Morris Water Maze impractical. Though this method could provide insight into group differences and cognition in a controlled cortical impact model of traumatic brain injury in mice, it can also be useful for measuring cognition in aged, and transgenic mouse models that are known to perform poorly in swimming based tests.On all testing days, perform the following preparatory steps. First, allow the mice to acclimate to the test room, while in their home cages for at least 30 minutes. The round maze features visual cues along the inner walls.The movable escape box positioned at one of nine different exit holes. While the mice acclimate, sanitize the exits and the box using a 70%ethanol spray. Next, fill the maze with roughly one inch of cold water.Keeping the water temperature consistent between trials is very important. So measure accurately, and adjust as needed. Now, position the escape box at one of the nine exit holes.Using a heating source to keep the box warm, ideally using a heating pad. Also, seal the box from light. The escape box should always be dark, warm and relatively odorless.The light source is also likely to be a cue so do not change its position between trials. Remove the test mouse from its cage gently by the tail, and place it in the center of the apparatus. Then immediately start timing how long it takes for the mouse to find the exit.If a mouse climbs into a terminating hole, and does not spontaneously reenter the maze after 20 seconds, do not stop the trial. Instead, guide the mouse back into the center of the maze by hand, and let the mouse complete the trial. If after three minutes, the mouse hasn't exited the maze, score the trial as a failure, and record the time as three minutes.Then by hand, carefully guide the animal along the straightest path to the exit. Once in the escape box, allow the mouse to remain there for one minute. Then transfer it back to its home cage while the maze gets reset.Between trials, thoroughly sanitize the escape box and exits with a 70%ethanol spray to prevent the mouse from using old factory cues to locate the correct escape route. This can be done pretty quickly. Now, repeat the trial on the same mouse twice more for a total of three consecutive trials.Every testing day consists of three trials per mouse. No more, and no less. In addition to sanitizing, drain the maze and refresh the water between testing different mice.Be sure to keep the water temperature between 12 and 14 degrees Celsius. Use containers of ice or colder hot water to adjust the tap water temperature into this range. Between testing days, it is important to make certain that the visual cues in the maze, and in the space surrounding the maze remain consistent.A complete testing regime includes five consecutive testing days all run in the same manner. The fifth day is considered the measure for memory retention. Provided no tests are performed between day six and 11, a test on day 12 can be used to measure long term memory.The radial water maze was used to investigate injury dependence spatial memory deficits in mice receiving either controlled cortical impact induced traumatic brain injury or a sham injury. The TBI surgery is described in detail in the text protocol and in a JoVE article by Romin, Gao and Chen from 2014. Briefly put, the injury was generated using a solenoid driven cortical impact with a three millimeter convex tip.The shams were operated on but impacted by the device. 35 days post surgery, the described testing regime was performed. All the mice passed the criteria test for a desire to escape the maze.So all were included in the analysis. The results show a clear difference between the TBI mice and sham controls. Escape latency was significantly longer for injured mice on the first day of training, and on both of the two memory test days.Thus, the described TBI affected the animal's capacity to learn. After watching this video, you should have a good understanding of how to properly perform cognition testing using a mouse specific test of spatial cognition. Once mastered, this technique can be done in less than 15 minutes per animal if it is performed properly.While attempting this procedure, it is important to remember that the positioning of visual cues and the water temperature must remain consistent across all trials.

Research

JoVE Journal

Behavior

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

Shallow Water Paddling Variants of Water Maze Tests in Mice

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 ...

科研

行为学

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 ...

The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents

双-H迷宫：一个强大的行为测试学习和记忆的鼠害

Spatial cognition research in rodents typically employs the use of maze tasks, whose attributes vary from one maze to the next. These tasks vary by their ...

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

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, ...

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

颅脑损伤后大鼠行为缺陷的检测

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

Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder

压力增强恐惧学习--创伤后应激障碍的健壮啮齿动物模型

Fear behaviors are important for survival, but disproportionately high levels of fear can increase the vulnerability for developing psychiatric disorders ...

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

一种新的小鼠目标识别与目标定位行为测试

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

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

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 ...

Inducing Post-Traumatic Epilepsy in a Mouse Model of Repetitive Diffuse Traumatic Brain Injury

在重复性扩散创伤性脑损伤小鼠模型中诱导创伤后癫痫

Traumatic brain injury (TBI) is a leading cause of acquired epilepsy. TBI can result in a focal or diffuse brain injury. Focal injury is a result of ...

Utilizing a Reconfigurable Maze System to Enhance the Reproducibility of Spatial Navigation Tests in Rodents

利用可重构的迷宫系统提高啮齿动物空间导航测试的可重复性

Several maze shapes are used to test spatial navigation performance and behavioral phenotypes. Traditionally, each experiment requires a unique maze ...