作者承认埃尔丁Jašarević先生，斯科特·威廉姆斯先生，罗杰·W·麦森先生，莎拉·A·约翰逊，R·迈克尔·罗伯茨博士，马克河Ellersieck博士和David C.基尔博士在大学密苏里州和C德尔伯特罗先生和照顾动物的工作人员在国家毒理学研究中心/美国FDA。这项工作是支持由美国国立卫生研究院资助的挑战，授予中国南车（RC1 ES018195），一个密苏里大学优势格兰特（CSR和DCG），密苏里大学学院兽医学院奖（CSR），并在国家中心协议E7318毒理学研究/ FDA认证。

1。巴恩斯迷宫手术小鼠害<ol><li>打开顶灯的迷宫和地方上面的“不输入”在实验室门的外侧的迹象。 </li><li>在正常的家庭笼带来小鼠试验室开始第一次审判，允许习惯之前大约30分钟到。如果房间很安静，它可能不是必要的，包括白噪声，否则预防措施可以考虑。 </li><li>设置跟踪程序。 </li><li>轻轻地从它的首页笼取出第一个鼠标，并放置在高大的盖塑料盒。将其转义（清洁家园）聚​​丙烯笼（29厘米×19厘米×13厘米）的指定的逃生孔下。 <ol><li>确保被阻断管从逃生孔移除，而所有其他孔被堵塞的纸张。 </li><li>画帘各地的迷宫。 </li></ol></li><li>将塑料盒用鼠标里面的迷宫中心，约8秒后，轻轻TA柯动物出笼子，并将其放置到迷宫。 <ol><li>把动物在迷宫的中心后，悄悄移动到电脑区域（〜150厘米的迷宫）。 </li><li>启动适当的跟踪软件程序应该已经打开，以确保最小的时间（几秒钟内）已经从动物置于迷宫直到程序开始记录其性能的时间已过。 </li></ol></li><li>从电脑显示器和记录孔数，试验次数，搜索策略，并提出错误数，观察动物的表现。一个错误的定义是嗅了不正确的孔。基于跟踪模式搜索策略的评估可以由活的或以后。 <ol><li>搜索策略被归类为直接 （直接进入逃生笼3或更少的错误）， </li><li> 串行 （沿迷宫周边行驶，直至逃生笼位），或</li><li> 随机&lt;/ STRONG&gt;（穿越迷宫中心多次检查各孔）。 </li></ol></li><li>停止跟踪程序，当动物有逃脱笼子里所有的四只爪子。 </li><li>如果鼠标没有在5分钟内进入逃生笼，轻轻地引导到正确的位置，进入逃生笼。让小鼠留在笼子逃生2分钟。 </li><li>从笼子里逃脱鼠标移除，并放置在家里的笼子。 </li><li>喷迷宫顶部和逃生笼用70％乙醇并擦干。运行其第二次试验前30分钟，一边将第一笼/鼠标。 </li><li>在开始下一个鼠标，请将先前正确的逃生孔，取出纸塞从该下一个主题指定的逃生孔堵孔。 </li><li>每个鼠标的2个试验/天约30分钟的试验间隔测试。 </li><li>重复这些步骤，直到所有的老鼠已经过测试，连续七天，这可能会增加的可能性Øf观察改进的性能和/或治疗组，相对于仅四天的数据之间的差异。 </li></ol> 2。巴恩斯迷宫检测大鼠当一个跟踪程序不可用<ol><li>确保迷宫是在正确的位置（直接在下面居中灯），挡住nonescape孔，防止动物闹翻了假底的牢固的迷宫，逃生笼在指定位置的第一个主题。顶灯迷宫上述应打开。 </li><li>确保电脑和相机已经准备就绪，提供了跑表功能。 </li><li>打开白噪声衰减来自其他附近地点的任何噪音。该测试仪的椅子是从迷宫上方最近的边缘约122厘米并保持在整个测试中相同的位置。 </li><li>定时器（设定为2分钟）应提供（只需要在测试的第1天）。计时器不应该“嘟”或以其他方式制造噪音。门（县）试验ROOM应该有“禁止进入”的牌子之外。 </li><li>测试顺序表科目将列出题目的测试，会话数，为每个主题逃生笼的孔数的位置和面积的顺序来记录延迟和天各科时间，以及一个地区的任何必要的注意事项（ 图6）。 </li><li>从30〜60分钟的第一个鼠要测试之前，使在其家笼中的动物的试验室，以允许习惯。 </li><li>中心管的老鼠是在审判开始时放入设置在迷宫中心。将纸板片显示在最前面的第一个动物的ID。这使得视频录制通过观察视频的前几秒钟捕捉动物标识，便于识别每科。 </li></ol>初步测试第1天： <ol><li>开始电脑视频录制器（如果使用）和包括约5秒，为主旨的动物标识表中的审判ECT鉴定。文件名（或创建日期）将确定测试的日期/时间。 </li><li>将其从笼中兽首（检查身份，如果多个动物在笼），轻轻放在第一头进入逃生笼。盖上笼逃生用一个额外的假底，并启动2分钟计时器。这使动物习惯于在笼逃生。 </li><li> 2分钟定时结束后，轻轻地从逃生仓卸下动物（除去虚假的底盖，以及与设置在离迷宫），电梯ID票据，并立即将大鼠中央管内。盖上纸板ID票据中心管的顶部。 </li><li>轻轻地，慢慢抬起中心管与纸板盖，备用。启动秒表为中心管的动物上面抬起。移动到坐在测试仪的椅子上。 </li><li>在椅子上静静地坐着，看着这两个动物和秒表。每个动物有最多5分钟以找到逃逸笼。 </li><li>如果大鼠找到逃逸笼中小于5分钟，停止秒表和记录的延迟和时间上的测试程序表。从逃生笼取出动物，并把回笼子。 </li><li>如果老鼠没有发现在5分钟内逃生笼，动物轻轻地引导到逃生笼，等待15秒，以消除和动物回到笼子前通过。 <ol><li>这15秒的时间可以用时钟的秒针在测试室的墙上定时。 </li><li>一天的测试顺序表和记录的大鼠没有找到逃生笼创纪录的时间。 </li></ol></li><li>如果老鼠下降/跳下迷宫，测试人员应该看一眼秒表的时间。然后，测试人员应该尝试快速检索动物。 <ol><li>如果这能在10秒内完成，替换动物到迷宫的中心，并记录在测试片（如果测试者可以跌倒或跳跃区分，这应该是表示）秋/跳跃的时间。继续试用。 </li><li>如果检索ANI正常所需的时间比10秒长，停止秒表，并把动物放回饲养笼。秋季/跳远纪录时间（如果测试人员可以下降或跳跃区分，注意这点）。 </li><li>从试验中，动物下降/跳下，不能在10秒内检索到的数据是从统计分析中被删去。 </li></ol></li><li>停止在电脑上的视频录制。记录有关审判的任何意见。 </li><li>拆下迷宫上方的任何尿或粪便，喷以70％的乙醇，并彻底擦干。删除逃生笼，清洁用70％乙醇。 </li><li>把干净的笼子逃脱在指定的位置下一个主题。有一个以上的逃生笼允许每个风干，以减少乙醇的气味。把干净的假底在上孔（这样所有，但一个洞有一个假底和一个孔包含逃生笼）。 </li><li>与在迷宫中心的下一个主题ID表中设置的中心管。开始录像在电脑上。 </LI&gt; <li>取出下一动物进行测试，放入笼逃生（如果天/第1节），并开始2分钟计时器（仅日/第1节）。继续从上面的步骤2。每位受试者接受试验的1 /日。 </li><li>在所有的动物进行测试，清洁和迷宫逃脱牢笼，关闭顶灯，和白噪声。卸下门（S）“请勿进入”的牌子（次）。 </li></ol> 2天至7测试<ol><li>设立试验室和迷宫测试，细节如上。 </li><li>在迷宫中心，在上面标识表设置中心管。开始录像。从家笼中取出第一个动物，并放入中心管。 </li><li>这个步骤区分2-7天从第1天，具体而言，在2-7天，受试者被直接放置到中心管去除从家笼和避让笼内的2分钟驯化期后尚未完成。 </li><li>重复步骤从上述步骤4开始。 </li></ol> 3。统计分析对于巴恩斯迷宫终点<ol><li>数据分析可能需要数统计检验。连续的变量，例如等待时间和错误率，可以分析裂区在空间和时间52。 </li><li>如果某些动物没有最大分配的时间内找到逃逸或家笼，延迟数据可以被指定为最大，并通过使用ProcLife测试中的SAS版本9.2软件分析进行分析。 <ol><li>这种统计方法是一种用于行为数据，其中有一个上限截止有用。 </li></ol></li><li>搜索策略数据可以通过使用重复测量设计用PROC GLIMMIX和SAS版本9.2软件分析进行分析。 <ol><li>这首先分析采用累计记录它链接和多项分布，例如，所有这三个搜索策略（随机，串口，和直接）被纳入分析。 </li><li>如果要判断动物学习使用更有效的搜索策略（直接），一个次生在这两个低效率的策略（随机和串行）相结合，并比对更高效的直接搜索策略可以执行的搜索策略三维分析。 </li><li>这后一种方法导致一个二项式分布，同时采用PROC GLIMMIX。 </li></ol></li></ol>

本文件是按照美国食品和药物管理局（FDA）的政策进行了审查和批准发布。批准并不意味着内容必然反映了FDA的立场或意见，也不提商品名称或商品的构成认可或推荐使用。本报告中的调查结果和结论是作者的，并不一定代表美国食品药品管理局的意见。作者没有竞争的利益和没有透露。

在巴恩斯迷宫测试程序的关键步骤包括：1）提供适当的轻度厌恶刺激来激励动物找到逃生笼，2）确保统一的条件都能够维持相同的动物试验（ 如测试时间，测试人员，外部噪声控制，及可能影响性能等的刺激），3），如果试验是记录，优化，并确保适当的视频记录和文件备份和4）清洗，用70％乙醇的迷宫，以除去试验之间嗅觉视频。 确定激励对象以找到逃生笼最好?...

空间学习和记忆的啮齿类实验动物首次评估与食品剥夺大鼠的导航小巷的迷宫找到食物增强剂1。几十年后，提出了一种空间参考记忆系统2。相反，工作记忆是指存储在测试会话或试验中，参考存储器是指存储器横跨测试阶段或临床试验，并更密切相关的长期记忆。 几种类型的迷宫已经发展成为在小型和大型啮齿动物这个海马依赖的空间学习和记忆（ 例如水迷宫，多个T-迷宫，放射臂迷宫和旱地迷宫）3-6无创性评估。在这里，我们重点的圆形平台或Barnes迷宫，由卡罗尔·巴恩斯博士7于1979年首次描述上。这个迷宫已经被用来测试空间航行学习记忆在广泛啮齿类动物模型，包括大鼠（RAttus家鼠），老鼠（ 小家鼠 ），鹿鼠（Peromyscus maniculatus bairdii），加州小鼠（Peromyscus加利福尼亚小 ），和hystricomorph啮齿类动物（ 如 degus [Octodon degus]）8-13。使用巴恩斯迷宫评估的其他物种包括美国蟑螂（ 美洲大蠊 ）14，玉米蛇（ 锦蛇雀雀 ）15， &#160;有鳞爬行动物（ 如边斑点蜥蜴[ 歌stansburiana]）16，和非人灵长类动物（ 如小鼠狐猴[Microcebus鼱 ]）17。在我们的实验室，巴恩斯迷宫性能已被用作神经毒性的指标发育双酚A（BPA）或乙炔基雌二醇（EE2）曝光9-1113之后。它也被普遍用于各种小鼠品系18-21的老化效应7,22-28评估行为表型，和阿尔茨海默氏病相关的画质icits在动物模型3,29-33，以及锻炼和饮食，环境和代谢改变34-42的影响。 的巴恩斯迷宫利用一个主要优点是，它诱导少应力在相对 ​​于水迷宫，如Morris水迷宫43的主体，虽然两者都可以诱导急性增加血浆皮质酮的浓度在小鼠44上 。作为一个旱地迷宫，巴恩斯迷宫可能会更ethologically相关陆地啮齿动物45。虽然水迷宫性能已被证明是在小鼠3,46,47到遗传改变更敏感，巴恩斯迷宫性能是某些其他改动48,49更加敏感。在啮齿类动物模型在水迷宫的使用是不可能的，巴恩斯迷宫可以提供空间记忆保留31的微调评估。轻度厌恶刺激通常用于巴恩斯迷宫（ 如灯不亮），然而，可能无法提供足够的动力为啮齿动物，找到逃逸笼45。此外，啮齿动物可以学习，如果他们不进入笼逃生时没有处罚。而不是积极寻找逃生笼因此，一些啮齿类积极探索迷宫的每个试验的持续时间长。如由肯纳德和半圆-Pak的24评论，这增加了勘探可以延长等待时间来定位逃逸笼，路径长度，和增加错误数量。因此，对多个参数，包括时延，误码率，时间在正确的和不正确的象限，速度花了，时间移动，时间休息，和搜索战略测量，可以统称为每个主体的空间航行学习记忆能力8一个更好的指标-10。此外，性能可以测量的延迟先找到逃生笼（主要指标）或延迟进入逃生笼（总指标）。有些自变量主编的性能主要措施是空间学习的一个更准确地反映比总的措施50。大多数研究中，包括这里所描述的实施例中，使用延迟进入逃逸笼，以确定错误率和搜索策略。此外，一些跟踪的软件系统有三点体检测系统，可以测量嗅探正确与不正确孔的频率。最后，迷宫必须彻底与审判之间的​​乙醇清洗，以除去嗅觉线索，可以提供线索或证明分心到后续的动物。 巴恩斯迷宫的设计而变化，但通常各具有12或20个潜在逃逸孔，其中只有一个引出到家庭或逃生笼。逃生笼可以是位于下方的迷宫顶部的逃生孔（用于迷宫没有围墙），或内置于迷宫周围的墙壁。该线索的大小从约16.5厘米的高度或宽度（米范围内变化阿塞拜疆）水平线21.6厘米宽放置从地板到房间墙上的迷宫外的天花板。 图巴恩斯迷宫设计的Peromyscus品种1-5显示的例子（ 图1）和老鼠（ 图2-5）。插头或假底部必须覆盖nonescape孔，以防止动物掉落走出迷宫。试验室的大小可以变化（约20 平方米 ），但它必须足够大以提供足够的空间迷宫，habituating动物的房间，可容纳一台计算机与视频的建立（如果使用），和一个地方对于实验者从迷宫装置，使得它们的存在不与动物的表现干扰坐在一个距离（至少〜122厘米）。逃生笼位置分配应各治疗组之间和性别平衡。而此处所描述的具体程序不包括旋转试验，以阻止使用帧内迷宫气味线索，一些研究之间的迷宫把这个程序50。在我们的程序中，迷宫擦拭干净，用试验之间的乙醇，以消除异味的线索。 在寻 ​​找逃生笼，三种类型的检索策略已被定义（最初称为“模式”巴恩斯7）：1）随机，操作上定义为通过孔穿越迷宫的中心路径分隔的局部搜索，2）串口，定义为系统的搜索连续孔在顺时针或反时针方向，以及3）直接或空间，定义为直接导航到正确的象限而不穿过迷宫中心多于一次，并与3个或更少的错误。一般情况下，反复试验，老鼠通常通过上市（随机，串行和直接）51的顺序搜索策略进展。而不逸出笼的探针试验也可以用来作为进一步的措施的存储器50。 该协议及代表此结果两种啮齿类（Peromyscus物种否则称为小型啮齿动物）和大鼠的开发工作。虽然这些一般的程序可能还持有近交系和/或远交系小鼠（ 小家鼠 ），其他研究应征询那些后者的18-21种潜在的方法论差异。

<table border="0" cellpadding="0" cellspacing="0" width="1285">
	<tbody>
		<tr height="21">
			<td colspan="4" height="21" style="height:22px;width:1287px;">NOTE: Those items that are for small rodents only are bolded. Those items that are for large rodents only are italicized. Items neither bolded nor italicized are for both.</td>
		</tr>
		<tr height="147">
			<td height="147" style="height:147px;width:335px;">Barnes Maze platform with 12 or 20 escape holes every 30&#176;. For rats, each hole is 10.5 cm in diameter and 4 cm from the maze top edge. For use with automated tracking programs, a black top for white rodents or a white top for pigmented rodents is needed. For mice and rats, this circular top is 95 and 122 cm in diameter, respectively.</td>
			<td>US Plastics Corp, Lima, OH</td>
			<td>42625</td>
			<td style="width:469px;">This is the top of the Barnes Maze and the surface that the rodent is placed upon. It can be constructed from a variety of materials (e.g. Plexiglas), but for endocrine disruptor work, polypropylene BPA-free material is optimal. One of the holes leads to the an escape cage; all other holes are blind-ending or false-bottomed. For the rat maze, small slides on the underside of the maze platform allow the escape cage and false bottoms to slide in.</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:335px;">2&#34; Polypropylene pipe plug (24) 
			2&#34; 90&#176; Black polypropylene elbow (12) 
			2&#34; x 6&#34; Polypropylene pipe nipple (1)</td>
			<td>US Plastics Corp, Lima, OH</td>
			<td style="width:215px;">30724 
			32086 
			30712</td>
			<td style="width:469px;">These are only necessary for the small rodent (e.g. mouse) Barnes Maze. These adaptations are either blind-ending tubes/elbows or one of the tubes is connected to the pipe nipple that then leads to the escape cage.</td>
		</tr>
		<tr height="41">
			<td height="41" style="height:42px;width:335px;">False bottoms for rat Barnes Maze</td>
			<td></td>
			<td style="width:215px;"></td>
			<td style="width:469px;">These were custom made of ABS plastic and vacuum molded for the rat maze apparatus.</td>
		</tr>
		<tr height="83">
			<td height="83" style="height:83px;width:335px;">Circular aluminum wall/barrier (50 cm high) around the maze</td>
			<td style="width:268px;">Ace Hardware, Columbia, MO</td>
			<td style="width:215px;"></td>
			<td style="width:469px;">In the case of small rodents (e.g.&#160;mice), this barrier prevents them from falling off the maze; the rat apparatus generally does not require this. The wall may not be needed for laboratory mice that are relatively tame.</td>
		</tr>
		<tr height="62">
			<td height="62" style="height:63px;width:335px;">Support stand for maze platform top</td>
			<td style="width:268px;">US Plastics Corp, Lima, OH</td>
			<td style="width:215px;">42625</td>
			<td style="width:469px;">The stand supports the maze platform top such that it is elevated above the floor (typically, 70-100 cm) to motivate the rodent to locate the escape cage. The stand can be constructed of any material.</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:65px;width:335px;">White noise</td>
			<td style="width:268px;">SleepMate Sound Conditioner, 
			Marpac, Rocky Point, NC</td>
			<td style="width:215px;">980A</td>
			<td style="width:469px;">Background noise may be used to block out peripheral acoustic cues that may confound Barnes Maze testing across trials and animals</td>
		</tr>
		<tr height="85">
			<td height="85" style="height:86px;width:335px;">Light fixtures and 300-500 watt bulbs encased in aluminum shells. For example, Utilitech 500-watt halogen portable work lights.</td>
			<td style="width:268px;">Ace Hardware or Lowes</td>
			<td style="width:215px;"></td>
			<td style="width:469px;">Bright lights provide a mildly aversive stimulus which motivate the rodent to locate the escape cage. The lights are generally suspended ~150 cm above the maze top.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:335px;">Escape cage. For small rodents, this can be a polypropylene cage (27.8 x 7.5 x 13 cm).</td>
			<td style="width:268px;">Ancare, Bellmore, NY</td>
			<td style="width:215px;">N40 PP</td>
			<td style="width:469px;">The rat escape cage here was custom built and has a ramp leading into the escape cage.</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:335px;">Opaque tube (rats only) (27 cm diameter; 23 cm height) with a piece of thick cardboard to cover the top.</td>
			<td style="width:268px;"></td>
			<td style="width:215px;"></td>
			<td style="width:469px;">The tube is placed in the center of the maze and the rat is placed into the tube from the top which is covered with the cardboard. A handle on the outside of the tube allows easier lifting of the tube, which then begins the trial. The tube can be constructed of any material, but should be opaque.</td>
		</tr>
		<tr height="61">
			<td height="61" style="height:62px;width:335px;">High resolution video camera (e.g.&#160;Panasonic Digital Video Camera)</td>
			<td style="width:268px;">Panasonic, Secaucus, NJ</td>
			<td style="width:215px;">ICV19458</td>
			<td style="width:469px;">The video camera is positioned overhead and records trials for later analysis.</td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:335px;">Extra- or intra-maze geometric cues made of high quality cardboard construction paper</td>
			<td style="width:268px;">Any office supply store, such as Staples.</td>
			<td style="width:215px;"></td>
			<td style="width:469px;">These visual cues orient the animal within the maze environment, providing cues as to the spatial location of the escape cage; in rats, extra-maze cues on the walls work well, whereas in small rodents that require a wall around the maze, intra-maze cues must be used.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:335px;">Black curtain to surround the maze (small rodents only)</td>
			<td style="width:268px;">Any fabric and crafts store, such as Jo-Ann Fabrics</td>
			<td style="width:215px;"></td>
			<td style="width:469px;">A black curtain is used in small rodents (especially wild species, e.g. Peromyscus) to maintain attention within the maze confines.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:335px;">70% ethanol</td>
			<td style="width:268px;">Fisher Scientific</td>
			<td>BP2818-4</td>
			<td style="width:469px;">After each trial, the maze top and escape cage are cleaned to eliminate potential odor cues for consecutively tested rodents.</td>
		</tr>
		<tr height="126">
			<td height="126" style="height:126px;width:335px;">Tracking software program, such as Ethovision, and computer with appropriate video card and substantial (1 TB or more) hard-drive space. Alternatively, videos can be recorded directly to the computer for later analysis using a program such as Win TV (Hauppauge Computer Works, Inc.).</td>
			<td style="width:268px;">Noldus (Leesburg, VA)</td>
			<td style="width:215px;"></td>
			<td style="width:469px;">Tracking software is required to analyze trials for latency to locate the escape cage, velocity, distance traveled, time spent resting, time spent moving, time spent in the correct versus incorrect quadrants, time spent around the escape hole, number of errors or entries into incorrect holes, and overall search strategy employed to find the escape cage.</td>
		</tr>
		<tr height="86">
			<td height="86" style="height:87px;width:335px;">External hard drives, such as Seagate or WD, with a minimum 1- 2 TB of memory</td>
			<td>Any office supply store, such as Staples.</td>
			<td></td>
			<td>Videorecordings should be backed up in at least one separate location.</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;">Videorecording program, e.g. WinTV program</td>
			<td style="width:268px;">Hauppauge Computer Works, Inc., 
			Hauppauge, NY</td>
			<td></td>
			<td style="width:469px;">If tracking software is not available at the time of the testing, 
			the trials should be video-recorded for later analysis</td>
		</tr>
	</tbody>
</table>

barnes maze testing strategies with small and large rodent models

空间学习和啮齿类实验动物的记忆往往是通过在迷宫，其中最流行的是水和旱地（巴恩斯）迷宫续航能力进行评估。在会话或试验改进的性能被认为是反映逃生笼/平台位置的学习和记忆。认为比水迷宫压力较小，巴恩斯迷宫是一个圆形的平台，上面一个相对简单的设计有几个洞在周边边缘等距。但所有的孔中的一个是假底或盲结束，而一个导致逃生笼。轻度厌恶刺激（ 如明亮的顶灯）提供动力，以找到逃生笼。潜伏期找到逃生笼可在会议期间进行测量，但额外的端点通常需要视频录制。从这些录像，使用自动跟踪软件可以生成各种端点类似于那些在水迷宫生产（ 例如&lt;/ em&gt;的行驶距离，速度/转速，时间在正确的象限中度过，花费的时间动/静息和确认延迟）。搜索策略（ 即随机的，串行，或直接）的类型可以分为好。巴恩斯迷宫建造和测试方法不同，可以为小型啮齿类动物，如小鼠和大啮齿动物，如老鼠。例如，在特迷宫的线索是有效的鼠，小的野生啮齿动物可能需要内部迷宫的线索与周围的迷宫视觉障碍。适当的刺激必须确定哪些激励啮齿动物找到逃生笼。双方巴恩斯和水迷宫可作为时间4-7测试试验通常需要检测改进学习和记忆能力（ 如较短的延迟或路径长度来寻找逃生平台或保持架）和/或实验组之间的差异耗时。即便如此，巴恩斯迷宫是一种广泛使用的行为评估测量空间的航行能力和他们受遗传，神经行为操作，或药物/毒物接触潜在干扰。

性成熟的雄性鹿鼠依赖于找到潜在的合作伙伴繁殖，这是整个环境中广泛传播增强空间导航能力。既产前和成人接触的睾丸激素在组织和激活此以后的成年男性行为53是必不可少的。因此，有人推测，早期接触内分泌干扰物，可能会扰乱稍后性状的男性。为了检验这一假设，雄性和雌性鹿小鼠经产妇的饮食发育暴露于BPA的一种植物雌激素饮食，积极控制雌激素（炔雌醇[EE2]）的一种?...

Watch this Scientific Journal Video about Barnes Maze Testing Strategies with Small and Large Rodent Models at JoVE.com

Barnes Maze Testing Strategies with Small and Large Rodent Models

在旱地巴恩斯迷宫被广泛用于测量响应于轻度厌恶刺激空间导航能力。连续多天，对照组的性能（ 如等待时间来寻找逃生笼）提高，表明正常的学习和记忆。大鼠和小鼠之间的差异必然要求，在这里详细的设备和方法的变化。

巴恩斯迷宫测试策略与小型和大型啮齿类动物模型

Spatial learning and memory of laboratory rodents is often assessed via navigational ability in mazes, most popular of which are the water and dry-land ...

barnes-maze-testing-strategies-with-small-and-large-rodent-models

Research

JoVE Journal

Behavior

41.3K 次观看.  University of Missouri. 在旱地巴恩斯迷宫被广泛用于测量响应于轻度厌恶刺激空间导航能力。连续多天，对照组的性能（ 如等待时间来寻找逃生笼）提高，表明正常的学习和记忆。大鼠和小鼠之间的差异必然要求，在这里详细的设备和方法的变化。 

视频: Barnes Maze Testing Strategies with Small and Large Rodent Models

Nest Building as an Indicator of Health and Welfare in Laboratory Mice

The minimization and alleviation of suffering has moral and scientific implications. In order to mitigate this negative experience one must be able to identify when an animal is actually in distress. Pain, illness, or distress cannot be managed if unrecognized. Evaluation of pain or illness typically involves the measurement of physiologic and behavioral indicators which are either invasive or not suitable for large scale assessment. The observation of nesting behavior shows promise as the basis of a species appropriate cage-side assessment tool for recognizing distress in mice. Here we demonstrate the utility of nest building behavior in laboratory mice as an ethologically relevant indicator of welfare. The methods presented can be successfully used to identify thermal stressors, aggressive cages, sickness, and pain. Observation of nest building behavior in mouse colonies provides a refinement to health and well-being assessment on a day to day basis.

We demonstrate the utility of nest building behavior in laboratory mice as an indicator of welfare. Nest scoring is a sensitive technique that is altered by temperature, illness, and aggression. The time to integrate into nest test (TINT) is a simple cage-side assessment that can detect postoperative pain.

The minimization and alleviation of  suffering has moral and scientific implications. In order to mitigate this  negative experience one must be able to ...

科研

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 ...

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

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 behavioral flexibility and required memory duration, the number of goals and pathways, and also the overall task complexity. A confounding feature in many of these tasks is the lack of control over the strategy employed by the rodents to reach the goal, e.g., allocentric (declarative-like) or egocentric (procedural) based strategies. The double-H maze is a novel water-escape memory task that addresses this issue, by allowing the experimenter to direct the type of strategy learned during the training period. The double-H maze is a transparent device, which consists of a central alleyway with three arms protruding on both sides, along with an escape platform submerged at the extremity of one of these arms.
Rats can be trained using an allocentric strategy by alternating the start position in the maze in an unpredictable manner (see protocol 1; &#167;4.7), thus requiring them to learn the location of the platform based on the available allothetic cues. Alternatively, an egocentric learning strategy (protocol 2; &#167;4.8) can be employed by releasing the rats from the same position during each trial, until they learn the procedural pattern required to reach the goal. This task has been proven to allow for the formation of stable memory traces.
Memory can be probed following the training period in a misleading probe trial, in which the starting position for the rats alternates. Following an egocentric learning paradigm, rats typically resort to an allocentric-based strategy, but only when their initial view on the extra-maze cues differs markedly from their original position. This task is ideally suited to explore the effects of drugs/perturbations on allocentric/egocentric memory performance, as well as the interactions between these two memory systems.

The goal of this protocol is to investigate spatial cognition in rodents. The double-H water maze is a novel test, which is particularly useful to elucidate the different components of learning, consolidation and memory, as well as the interplay of memory systems.

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 ...

Testing Sensory and Multisensory Function in Children with Autism Spectrum Disorder

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are now recognized as a core symptom in autism spectrum disorder (ASD). Our ability to perceive and interact with the external world is rooted in sensory processing. For example, listening to a conversation entails processing the auditory cues coming from the speaker (speech content, prosody, syntax) as well as the associated visual information (facial expressions, gestures). Collectively, the &#8220;integration&#8221; of these multisensory (i.e., combined audiovisual) pieces of information results in better comprehension. Such multisensory integration has been shown to be strongly dependent upon the temporal relationship of the paired stimuli. Thus, stimuli that occur in close temporal proximity are highly likely to result in behavioral and perceptual benefits &#8211; gains believed to be reflective of the perceptual system&#39;s judgment of the likelihood that these two stimuli came from the same source. Changes in this temporal integration are expected to strongly alter perceptual processes, and are likely to diminish the ability to accurately perceive and interact with our world. Here, a battery of tasks designed to characterize various aspects of sensory and multisensory temporal processing in children with ASD is described. In addition to its utility in autism, this battery has great potential for characterizing changes in sensory function in other clinical populations, as well as being used to examine changes in these processes across the lifespan.

We describe how to implement a battery of behavioral tasks to examine the processing and integration of sensory stimuli in children with ASD. The goal is to characterize individual differences in temporal processing of simple auditory and visual stimuli and relate these to higher order perceptual skills like speech perception.

测试儿童的感官和多感官功能自闭症谱系障碍

In addition to impairments in social communication and the presence of restricted interests and repetitive behaviors, deficits in sensory processing are ...

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 ...

Testing Animal Anxiety in Rats: Effects of Open Arm Ledges and Closed Arm Wall Transparency in Elevated Plus Maze Test

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral science, conflicting outcomes are often provided from different laboratories. To identify reasons for the different outcomes, we previously focused on arm features, which differ between laboratories, most notably the presence/absence of ledges at the sides of open arms and the transparency/opaqueness of closed arm walls. In a previous report, we used a custom designed container to compare rat behavior on different combinations of open and closed arm designs under otherwise identical experimental conditions, and showed that differences in arm features interfere with experimental outcomes. In brief, open arm ledges significantly increased anxiety-like behavior in rats, while transparent arms may also have decreased this behavior. Furthermore, we verified a higher detection sensitivity of the effect of an anxiolytic drug in a combination of no-ledged open arm + opaque walled closed arm compared with a combination of ledged open arm + transparent walled closed arm. In this report, we introduce our protocol for the elevated plus maze test, together with discussion of the key results from the previous report and our experimental experience. We believe this report will provide useful information for researchers who have employed or who plan to use the elevated plus maze in their studies.

Rats' anxiety-like behavior tested by the elevated plus maze varies highly depending on the testing environment. Here we show how apparatus settings, especially arm structure, affect behavior on the maze, and we explain a reliable protocol to detect effects of anxiolytic drugs. This report will contribute to anxiety research.

大鼠动物焦虑症的实验研究: 开放臂壁和闭合臂墙透明度对高加迷宫试验的影响

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral ...

Utilizing the Modified T-Maze to Assess Functional Memory Outcomes After Cardiac Arrest

Background: Evaluating mild to moderate cognitive impairment in a global cerebral ischemia (i.e. cardiac arrest) model can be difficult due to poor locomotion after surgery. For example, rats who undergo surgical procedures and are subjected to the Morris water maze may not be able to swim, thus voiding the experiment.
New Method: We established a modified behavioral spontaneous alternation T-maze test. The major advantage of the modified T-maze protocol is its relatively simple design that is powerful enough to assess functional learning/memory after ischemia. Additionally, the data analysis is simple and straightforward. We used the T-maze to determine the rats&#39; learning/memory deficits both in the presence or absence of mild to moderate (6 min) asphyxial cardiac arrest (ACA). Rats have a natural tendency for exploration and will explore the alternate arms in the T-maze, whereas hippocampal-lesioned rats tend to adopt a side-preference resulting in decreased spontaneous alternation ratios, revealing the hippocampal-related functional learning/memory in the presence or absence of ACA.
Results: ACA groups have higher side-preference ratios and lower alternations as compared to control.
Comparison with Existing Method(s): The Morris water and Barnes maze are more prominent for assessing learning/memory function. However, the Morris water maze is more stressful than other mazes. The Barnes maze is widely used to measure reference (long-term) memory, while ACA-induced neurocognitive deficits are more closely related to working (short-term) memory.
Conclusions: We have developed a simple, yet effective strategy to delineate working (short-term) memory via the T-maze in our global cerebral ischemia model (ACA).

This protocol describes the use of a modified T-maze to evaluate functional learning/memory in asphyxia cardiac arrest-induced cerebral ischemia.

应用改良 T 迷宫评估心脏骤停后的功能记忆结果

Background: Evaluating mild to moderate cognitive impairment in a global cerebral ischemia (i.e. cardiac arrest) model can be difficult due to poor ...

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. ...

Elevated Plus Maze Test Combined with Video Tracking Software to Investigate the Anxiolytic Effect of Exogenous Ketogenic Supplements

The overall goal of this study is to describe the methodology of the elevated plus maze (EPM) test in combination with a video tracking software. The purpose of the method is to document the effect of various potential anxiolytic treatments on laboratory rodent models. The EPM test is based on the rodents&#39; proclivity toward protected, enclosed dark spaces and unconditioned fear of open spaces and heights, and their innate intense motivation to explore novel environments. The EPM test is a widely used behavioral test for investigating the anxiolytic or anxiogenic responses of rodents given drugs that are known to affect behavior. Observation demonstrating a decreased proportion of time spent on closed arms, an increased proportion of time spent on open arms, a reduced number of entries to closed arms, and an elevated number of entries to open arms measured by the EPM test may reflect reduced anxiety levels. Using this method, the effect of exogenous ketone supplements on anxiety-related behavior is tested in Sprague Dawley (SPD) rats. Exogenous ketone supplements are chronically fed to the rats for 83 days or subchronically and acutely orally gavaged, daily for 7 days, before conducting the EPM test. Behavioral data collection is performed using the SMART video tracking system by a blinded observer at the end of the treatments. The main findings indicate that the EPM test is an effective method to detect the ketone supplement-induced anxiolytic effect and can be considered a sensitive measure to assess changes in anxiety behavior associated with drug- or metabolic-based therapies.

Here, we present a protocol to investigate changes in the anxiety level of rodent animal models. The elevated plus maze (EPM) test, used together with a video tracking software, provides a reliable method to document the effect of various potential anxiolytic treatments in preclinical laboratory scenarios.

高架加迷宫试验结合视频跟踪软件研究外源性生酮类补充剂的毒性作用

The overall goal of this study is to describe the methodology of the elevated plus maze (EPM) test in combination with a video tracking software. The ...