我们要感谢新希望研究基金会继续支持和资助我们的调查。我们还要感谢理事会对这项工作的部分财政支持。

本文所述的所有协议都是按照女王大学动物保育委员会的批准进行的。行为测试的频率可以是每周或每月, 或者是两个的组合 (即,每周一次, 当你期望看到最大的差异, 每月在别处)。
注意: 小鼠的行为研究主要是性/年龄/应变依赖性, 因此, 必须收集适当的时间点, 并保持一致的跨实验组。环境因素 (例如,气味、噪音、温度、湿度照明、等) 极大地影响了小鼠的行为和焦虑。尽量减少这些环境因素。
1. 野外试验
注意: 在进行行为测试之前, 动物应该习惯于测试开始前 10-15 分钟的房间。确保行为测试协议遵循适当的个人防护设备和所有当地设施的指导方针。
注: 测试前不进行培训。
<ol><li>确保计算机和经常程序已打开、正在运行, 并正确连接到照相机或开放域框。单击 smartware 程序、打开字段图标和 "确定"。从摄像机选项中选择了 "数字模拟转换器" 源。点击 "检测", 并确保整个开放领域的空间是可视化的, 尺寸是 30 cm x 30 厘米。 注意: 设备布局可能会因空间限制而异, 但要确保计算机和开放的现场设备在光线充足的房间内彼此接近, 以便进行适当的视频捕获。</li>
	<li>单击 "校准"、"快照", 然后 "确定" 以确保在打开的域范围内检测到鼠标。单击 "时间" 以预先设置测试鼠标的时间量;在这种情况下, 设置5分钟。</li>
	<li>通过单击 "主题" 图标输入主题。单击 "计划程序", 并突出显示所有测试对象, 然后单击 "双绿色箭头" 和 "第一阶段, 第一节"; 这将带来所有的主题, 以开始收集数据。</li>
	<li>将鼠标放在打开字段的中心, 然后单击 "开始" 图标以提示程序开始录制。一次只测试一只老鼠。</li>
	<li>一旦5分钟完成, 程序将自动移动到下一个主题。在这种情况下, 请移除已完成测试的鼠标, 并将下一个主题放到打开的字段中。单击 "开始"。</li>
	<li>把设备擦干净对其余的测试对象重复步骤 1.3-1.4。</li>
	<li>为了在所有的实验对象都经过测试后分析数据, 点击屏幕右上方的 "分析" 图标。再次单击 "分析", 然后 "汇总报告"。(可选) 将数据导出到 USB 上。</li>
</ol>2. 网格测试
注: MT 的表面面积和网格大小可能会影响性能。在 MT 上, 如果一只老鼠在第一个十年代的第一个2收集时间点内脱落, 它们将立即被放回网格上进行第二次尝试。这里使用的网格是一个金属丝网, 网孔直径约1.5 毫米。
注意: 建议在一天的同一时间运行这些测试, 因为生理和生物化学参数在一天中波动。体重可能影响这项试验的表现, 因此必须加以考虑。
<ol><li>将鼠标放在网格的中心, 并将网格翻转到至少20厘米以上的透明容器上。一旦反转, 启动计时器。</li>
	<li>时间和记录的滞后时间下降。如果鼠标不属于六十年代, 给它一个分数六十年代和不进行进一步的试验。允许鼠标至少休息5分钟。这是1审判的结束。</li>
	<li>擦拭设备, 并在5分钟内试验间隔, 如果需要, 测试第二个鼠标。重复步骤 2.1-2.2 为试验2和 3, 如果需要 (只要鼠标不得分六十年代, 它应该接受三试验)。</li>
</ol>3. Rotarod 测试
注: 在 RT 上的杆的表面和直径可能会影响性能。在 RT 上, 如果一只老鼠在第一个十年代的第一个2收集时间点内脱落, 就把它立即放回标尺上进行第二次尝试。
注意: 建议在一天的同一时间运行这些测试, 因为生理和生物化学参数在一天中波动。体重可能影响这项试验的表现, 因此必须加以考虑。
<ol><li>打开理事会 rotarod 和计算机。确保它们已正确连接以进行数据记录。</li>
	<li>确保程序正在运行加速协议。将 rotarod 测试的所需长度设置为 xxx (有效范围为000到 999);在这种情况下, 按 300 *。设置用于 xxx 的车道数 (有效范围为001到 005);在这种情况下, 按 005 *。将起始速度设置为 xxx rpm (输入3005作为 5 rpm; 有效范围为001到 045);在这种情况下, 按 004 *。</li>
	<li>将最高速度设置为 xxx rpm (输入4030为 30 rpm; 有效范围为001到 045);在这种情况下, 按 040 *。将坡道速度设置为 xxx (输入5030以使30秒的坡道进入最高速度; 有效范围为000到 999);在这种情况下, 按 300 *。将单元设置为鼠标模式 (输入6001用于鼠标前进, 6002 用于鼠标反转);在这种情况下, 按 6001 *。</li>
	<li>在开始试验之前, 确保所有磁化车道都是平衡的。将一只老鼠放在 rotarod 的每条车道上。</li>
	<li>按 "开始" 启动程序。当老鼠倒下时, 立即把它们从车道上移开, 以确保它们不会 "绊倒" 其他车道。</li>
	<li>允许老鼠休息10分钟的间隔试验时间。这是1审判的结束。在试验间隔时间内, 擦拭设备, 开始试验下一组小鼠。</li>
	<li>根据需要重复步骤 4-6。如果鼠标停留在 rotarod 上进行完整的5分钟试验, 则不需要对该鼠标进行进一步的试验。</li>
</ol>

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作者没有什么可透露的。

对所有的测试, 清洁和消毒的表面, 以尽量减少感染和干扰的小鼠。同时, 在使用经常、RR 和 MT 时, 一定要让老鼠在试验之间和行为测试之间有足够的休息时间。
在经常的情况下, 关键的是每个鼠标都放在开放字段的中间, 并在鼠标释放到中心时启动程序。确保没有手的动作, 传感器可以注册后启动程序。
对于 MT, 重要的是有一个屏障之间的网格区域的鼠标?...

行为测试的目的是测量表型特征, 无论是研究新的小鼠模型的疾病影响中枢神经系统或试用新的治疗。有各种各样的行为测试可供选择。使用行为测试组合的基本原理通常是充分评估临床治疗前的结果。行为测试的电池包括开放现场测试 (经常), 网格测试 (MT) 和 rotarod 测试 (RR)。
常用于一般运动活动的测量1,2,3,4,5,6,7。此评估允许鼠标在一个开放的领域自由移动, 并采取的测量是鼠标在行为试验过程中的动作。使用一个经常包括饲养, 距离移动, 时间花费移动 (例如,行走和跑步) 和活动随着时间的变化 (例如,跳跃和慢/多动运动) 的定量分析, 这就是为什么它是一个有用的和彻底分析啮齿动物的行为。
MT 用于评估鼠标的强度1,2,8,910。使用所有的四肢体挂断铁丝网网格允许非侵入性测量的能力的小鼠表现出持续的肢体张力, 而反对的影响重力。这一评估是通过把鼠标放在一个倒置的网格上, 并定时它的滞后时间下降。这项测试通过测量在脱落前它能在倒置的屏幕上保持多久来评估鼠标的肌肉强度。
RR在使用加速协议1、2、7、8、9、1213中评估鼠标的协调性。rotarod 装置由一个圆柱形光束组成, 在空气中旋转 4 rpm。鼠标可以学习这种运动协调的技能, 然后由缓慢, 增量增加到 40 rpm 挑战。经典的, 恒定速度协议是衡量肌肉力量, 而加速的协议为 RR 评估协调, 耐力和肌肉力量1,2,7,14。
这三行为测试的优点是, 他们被广泛接受的整个啮齿动物行为测试社区2,7,8,9, 当采取不只是作为总和个别测试, 但总的来说, 他们可以被用来作为一个全球评估的表型行为时, 调查不同的结果, 实验治疗。经常是唯一的测试为整体运动活动2。RR 也是评估协调2的唯一方法之一, 而不是使用步态分析软件, 这在这里不会讨论。有几种方法可以评估老鼠的肌肉强度;然而, 使用 MT, 或线挂测试, 已被普遍使用的文献和被接受为可靠的方法测试肌肉力量2,8,9,10,11. 测量一般运动和协调的许多其他技术非常耗时, 可能不会产生可靠的数据 (例如,手动定时鼠标移动或手动绘制用于步态分析的爪子)。自动系统的经常和 RR 增加了数据的可靠性和有效性, 并节省了时间和精力。
例如, 考虑到山德霍夫病小鼠模型的神经, 在执行这一测试电池时, 经常会是这些测试的第一个, 用来评估通常在3月大的时候从这个小鼠模型中看到的运动异常。在12周的年龄, 运动协调方面的赤字也应该开始显现。肌肉力量的缺陷应该在14周的年龄开始, 但最终会比16周更重要。
这些测试是有用的, 当研究导致重大运动损伤的疾病, 包括神经退行性疾病9如山德霍夫疾病1,8,13, 帕金森病7,亨廷顿氏病多发性硬化症这些测试还可以用来研究衰老, 并进行比较的老年评估或健康测量。步态紊乱和运动和平衡的变化在许多这些疾病状态中被看到。然而, 这些测试的用处并不局限于有普遍神经肌肉症状的疾病。
请注意, 在动机或任何被描述的行为测试措施的新奇性方面, 都没有发现混杂变量。在老鼠显示出任何表型症状之前, 研究者获得初步的行为数据是某些疾病状态和病症的必要条件;研究员应该周期性地 (每周) 保证所有马达损伤被交代。许多疾病有快速出现的表型症状, 没有每周的测试, 这些症状不会被占。

<table><tbody><tr><td>IITC Life Sciences Rotarod with Series 8 computing software&amp;nbsp;</td><td>IITC Life Sciences</td><td>755</td><td></td></tr><tr><td>Square Open Field 45 x 45 x 40 cm (grey color). Other floor color available: white, black.</td><td>Harvard Aparatus (PanLab)</td><td>760190</td><td></td></tr><tr><td>&amp;nbsp;Open Field Preconfigured Module</td><td>Harvard Aparatus (PanLab)</td><td>760688</td><td></td></tr><tr><td>Smart V3.0 Software Platform&amp;nbsp;</td><td>Harvard Aparatus (PanLab)</td><td>760681</td><td></td></tr><tr><td>Video converter (analog/digital)</td><td>Harvard Aparatus (PanLab)</td><td>760262</td><td></td></tr><tr><td>Roof fixing sys for camera</td><td>Harvard Aparatus (PanLab)</td><td>760277</td><td></td></tr><tr><td>Analog Sony Camera &amp;amp; lenseNTSC</td><td>Harvard Aparatus (PanLab)</td><td>760505</td><td></td></tr></tbody></table>

battery of behavioral tests assessing general locomotion, muscular strength, and coordination in mice

行为测试用于临床前试验, 以评估特定疾病或治疗对动物的福祉和健康的表型效应和结果。有许多行为测试可以应用。我们选择了一般运动测试, 野外测试 (经常);肌肉强度的测试, 网格测试 (MT);和测试的协调, rotarod 测试 (RR)。测试可以在每周或每月的基础上完成。作为一般运动的一个测试, 经常工作通过客观地监测运动参数, 而鼠标是在野外设备。该领域通常是一个 2 ' x 2 ' 盒, 并通过激光传感或视频捕获记录的运动。鼠标放在开放字段的中心, 允许自由移动以进行测试。MT 使用鼠标从一个倒置的屏幕上掉下来作为衡量肌肉力量的时间。将鼠标放在屏幕上, 在一个清晰的框上反转, 并定时等待它们的滞后时间下降。进行了三项试验, 最好的三项试验是在当天取得的。六十年代的分数是鼠标左倒的最长时间。在网格测试试验中, 给老鼠5分钟的休息时间。最后, 关于 RR 的加速的协议评估马达协调和耐力。在试验中, 鼠标在旋转杆上行走, 因为它在转速从 4 rpm 增加到 40 rpm 超过5分钟。试验结束时, 鼠标接触磁化压力传感器后下降。每只老鼠经历了三次试验, 最好的试验是在那一天取得的。这种综合行为数据允许对测试动物的移动性、协调性、强度和运动进行全球评估。在三行为测试措施中, 至少有两项必须表现出对动物的改进, 以使其具有整体改善运动功能的资格。

研究动物可以每周或每月接受行为测试范式, 以适应分析所需的必要时间点。有关行为测试计时的示例, 请参见图 1 。在下面的代表性数据中, 取自 Osmon et al。(2016), 小鼠每月接受行为测试, 从12周开始, 直到他们的人性化终点大约40周龄。行为测试的时间对实验来说有时是至关重要的, 特别是当未经处理的与经过治疗的动物的生存范围很广并且需要进行比?...

Watch this Scientific Journal Video about Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice at JoVE.com

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

行为测试用于临床试验, 以评估疾病或治疗对动物福祉的表型影响。为了在全球范围内评估电机的功能, 我们选择了一般运动, 肌肉力量和协调的测试: 开放现场测试, 网格测试, 和 rotarod 测试, 分别。

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 ...

battery-behavioral-tests-assessing-general-locomotion-muscular

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

13.5K 次观看.  Queen's University. 行为测试用于临床试验, 以评估疾病或治疗对动物福祉的表型影响。为了在全球范围内评估电机的功能, 我们选择了一般运动, 肌肉力量和协调的测试: 开放现场测试, 网格测试, 和 rotarod 测试, 分别。

视频: Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

帕金森氏症小鼠模型的感觉功能评估

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

科研

行为学

Measuring the Strength of Mice

Kondziela7 devised the inverted screen test and published it in 1964. It is a test of muscle strength using all four limbs. Most normal mice easily score maximum on this task; it is a quick but insensitive gross screen, and the weights test described in this article will provide a finer measure of muscular strength.
There are also several strain gauge-based pieces of apparatus available commercially that will provide more graded data than the inverted screen test, but their cost may put them beyond the reach of many laboratories which do not specialize in strength testing. Hence in 2000 a cheap and simple apparatus was devised by the author. It consists of a series of chain links of increasing length, attached to a "fur collector" a ball of fine wire mesh sold for preventing limescale build up in hard water areas. An accidental observation revealed that mice could grip these very tightly, so they proved ideal as a grip point for a weight-lifting apparatus. A common fault with commercial strength meters is that the bar or other grip feature is not thin enough for mice to exert a maximum grip. As a general rule, the thinner the wire or bar, the better a mouse can grip with its small claws.
This is a pure test of strength, although as for any test motivational factors could potentially play a role. The use of scale collectors, however, seems to minimize motivational problems as the motivation appears to be very high for most normal young adult mice.

Deficits in muscular strength occur in many clinical conditions such as motor neuron disease. The inverted screen and weight lifting tests described here measure strength in mice almost exclusively, with minimal influence of factors such as coordination.

强度测量小鼠

Kondziela7 devised the inverted screen test and published it in 1964. It is a test of muscle strength using all four limbs. Most normal mice easily score ...

医学

Assessment of Motor Balance and Coordination in Mice using the Balance Beam

Brain injury, genetic manipulations, and pharmacological treatments can result in alterations of motor skills in mice. Fine motor coordination and balance can be assessed by the beam walking assay. The goal of this test is for the mouse to stay upright and walk across an elevated narrow beam to a safe platform. This test takes place over 3 consecutive days: 2 days of training and 1 day of testing. Performance on the beam is quantified by measuring the time it takes for the mouse to traverse the beam and the number of paw slips that occur in the process. Here we report the protocol used in our laboratory, and representative results from a cohort of C57BL/6 mice. This task is particularly useful for detecting subtle deficits in motor skills and balance that may not be detected by other motor tests, such as the Rotarod.

Deficits in fine motor coordination can be assessed with the balance beam test. Performance on the beam is quantified by the speed at which the beam is traversed and the number of times the mouse slips on the beam.

在小鼠体内的汽车平衡和协调的评估使用的平衡木

Brain injury, genetic manipulations, and pharmacological treatments can result in alterations of motor skills in mice.  Fine motor coordination and ...

神经科学

Measuring Motor Coordination in Mice

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance2. 
Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available.
The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. 
Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test12 or the Catwalk (Noldus)15 apparatus are generally used to assess motor coordination in rats.

Protocols are presented for two established motor coordination tasks, the accelerating rotarod and horizontal bar, also two tests developed in Oxford recently, the static rods and parallel bars. These tests can detect motor impairments potentially of interest in their own right, as well as being possible variables in tests of other areas of behavior.

测量小鼠运动协调

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such ...

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

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

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

一种用于小鼠运动技能、情绪和认知重复评估的行为测试电池

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

<meta charset="utf8"></head><body>使用梯形梁测试评估 TH 相关小鼠模型中的运动性能

A Versatile, Behavioral Method to Investigate Thyroid Hormone Effects on Cerebellar Function

Thyroid hormone (TH) action is essential during the development of the central nervous system, including the cerebellum. In case of TH deficiency in early life such as congenital hypothyroidism, patients display neurological disorders such as cognitive retardation and motor deficits. There are various studies using mouse models with tissue- or cell-specific TH deficiency to investigate the role of TH in the cerebellum. Compared to generalized congenital hypothyroid mice, cerebellar cell-specific TH-deficient mice display milder and subtler ataxic features, making the assessment of motor function difficult when using conventional tests such as the rotarod test. 
Due to the need for an alternative tool to assess motor function in TH-related animal models, we developed a versatile behavioral method called the "ladder beam test," in which we can design the various ladder tests depending on the severity of ataxia in model mice. We utilized transgenic mice expressing a dominant-negative TH receptor specifically in the cerebellar Purkinje cell, a sole output neuron in the cerebellar cortex modulating motor performance. The newly-built ladder beam test successfully detected robust impairments in motor performance in the transgenic mice at a greater level compared to the rotarod test. Disruption of motor learning was also detected in the ladder beam test but not in the rotarod test. The protocol with this novel behavioral apparatus can be applied to other animal models that may show mild ataxic phenotype to examine subtle changes in cerebellar function.

<meta charset="utf8"></head><body>作者聚焦:准确评估小鼠甲状腺激素驱动的运动改变

Here we present a protocol for a versatile behavior test developed recently, the ladder beam test. This test has the advantage of detecting subtle cerebellar ataxia caused by a defect of thyroid hormone action in the central nervous system over the conventional behavior tests assessing motor performance.

一种研究甲状腺激素对小脑功能影响的通用行为方法

Thyroid hormone (TH) action is essential during the development of the central nervous system, including the cerebellum. In case of TH deficiency in early ...

使用行为测试验证 Angelman 综合征的小鼠模型

Behavioral Characterization of an Angelman Syndrome Mouse Model

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of AS. We use the rotarod learning paradigm, detailed gait analysis, and nest building test to detect and characterize animal motor impairments. We test animal emotionality in the open field and elevated plus maze tests, as well as the affect in the tail suspension test. When AS mice are tested in the open field test, the results should be interpreted with care, since motor dysfunctions influence mouse behavior in the maze and alter activity scores.
The reproducibility and effectiveness of the presented behavioral tests has already been validated in several independent Uba3a mouse lines with different knockout variants, establishing this set of tests as an excellent validation tool in AS research. Models with the relevant construct and face validity will warrant further investigations to elucidate the pathophysiology of the disease and grant the development of causal treatments.

作者聚焦:用于验证 Angelman 综合征小鼠模型的一系列高度可重复的行为测试 

This manuscript presents a set of highly reproducible behavioral tests to validate an Angelman syndrome mouse model.

安格曼综合征小鼠模型的行为表征

This manuscript describes a battery of behavioral tests available to characterize Angelman syndrome (AS)-like phenotypes in an established murine model of ...

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

摘要

探索更多视频

此视频中的章节

帕金森氏症小鼠模型的感觉功能评估

强度测量小鼠

在小鼠体内的汽车平衡和协调的评估使用的平衡木

测量小鼠运动协调

一种用于小鼠运动技能、情绪和认知重复评估的行为测试电池

一种研究甲状腺激素对小脑功能影响的通用行为方法

一种研究甲状腺激素对小脑功能影响的通用行为方法

一种研究甲状腺激素对小脑功能影响的通用行为方法

安格曼综合征小鼠模型的行为表征

安格曼综合征小鼠模型的行为表征