This work was supported by an Ontario Mental Health Foundation grant to B.S, and an Ontario Graduate Scholarship to M.K.

所有的程序都是由加拿大麦克马斯特大学动物护理委员会批准，并按照设定由动物保健的加拿大理事会的指导方针进行。 1.一般程序<ol><li> ，观察者小鼠1-2周，以现有的12小时亮/暗循环（ 例如，上午8点-下午8点）。黑暗周期中执行所有的程序和测试，与RT，湿度和光照强度是相对恒定的。 </li><li>标记或尾纹身所有小鼠，方便，数值识别较长期和1-2小时的每日处理他们在5-7天。 </li><li>直肠温度，体重和食物/水的摄入量的重复每日测量来检测诱导的老化或疾病进展的潜在发烧和/或营养不良。标准的排除标准包括低体重，由于减少了食物/饮水量，弯腰驼背的姿势皱皮，脑积水，眼睛周围卟啉放电等 </li><li>以便识别Ÿ神经功能障碍，可能混淆的整体活动和性能，执行标准感觉测试，如后肢夹紧反射13，视觉定位反射14，趋地性测试15，公文筐测验16，梁行走试验17-19，旋转杆20和嗅觉测试21。 注：该结果还可以帮助相关分析与INBEST措施，更精心挑选的其他程序（ 例如 ，Morris水迷宫，如果老鼠是如果老鼠是hyposmic /嗅觉缺失盲目，新物体的测试），降低组内的变异，以及排除小鼠出生缺陷或感染。 </li><li>清洁的塑料和玻璃装置用消毒剂以除去尿道同时测试从实验组和对照组的小鼠以交替的方式。 </li></ol> 2.综合行为站（INBEST）程序<ol><li>首页笼成立<ol><li>填写食物饮水机s的20毫克小鼠食物颗粒。 </li><li>灌装瓶用自来水。 注意：第二个瓶子可填充有感兴趣的溶液中，例如蔗糖或糖精溶液为偏爱测试。 </li><li>称取瓶来计算消耗在会议结束时的音量。 </li><li>将奶瓶嘴到lickometers。确保喷嘴不阻挡红外线传感器;如果这样做，减少喷口的长度。 </li><li>将候车亭在家里笼的选择角落。 </li></ol></li><li>计算机设置 注：在步骤2.2-2.11提供的软件命令相关的Ethovision XT 8.5软件包和试验条件在我们的实验室（材料/设备的列表中指定）。 <ol><li>照亮房间弥漫，昏暗的灯光下，其足以用于视频跟踪，但不反射离开框，地板或墙壁。 </li><li>打开默认视频跟踪项目，并成立了实验设置，通过键控相关细节（ 例如 ，日期/学习，组分配，房间条件等的时间）。随后，选择合适的视频源（PICOLO勤奋采集卡），数字领域（4），跟踪点（中央重点，nose-和尾点），测量（厘米，秒，度）为单位。 </li><li>在设置中选择试用列表选项卡后，通过单击Add按钮试验（1）定义试验的次数。接下来，指定使用添加变量按钮独立变量（ 如鼠标ID，性别，组分配，应变）。 </li><li>点击竞技场设置选项卡，并从现场视频拍摄的背景图像。通过使用适当的绘图工具（如创建矩形/折线/椭圆形），概述了外周边限定的各个赛场的参数。 </li><li>接下来，单击添加区组按钮，并概述了不同区域（ 如地板，lickometers，食品饮水机，攀登网添加感兴趣区<e米&gt;等）以相同的方式。添加隐藏的区域为那里的鼠标无法看到的领域（ 如住房和跑轮， 图2），单击添加隐藏区组按钮。确保指定的入口/出口并与每个隐藏区。 </li><li>每一个竞技场重复步骤2.4-2.5。通过突出校准和使用适当的工具（创建校准刻度/轴），以提供舞台的宽度和长度进行舞台校准。最后，通过单击验证竞技场设置按钮确认竞技场设置。 </li><li>突出审判控制设置选项卡，指定开始/停止条件和试验长度。设置启动条件时，中心点的时间超过1秒，在竞技场开始。操控测试期间通过扩大停止状态框，设置审理的延迟后终止，如10小时。 </li><li>根据检测设置选项卡中，突出显示相应的检测方法（ 如：动态减法和基于模型）。 </li><li>接下来，通过单击检测选项卡中设置按钮并按下抓取当前按钮抢空舞台上的参考图像。 </li><li>调整的对比度，使得中心，鼻子和尾部基于检测每只小鼠是可靠的，准确的和连续的范围内。对于小白鼠，指定鼠标比背景更亮比背景，暗如果使用色素的压力。 注：主体大小和视频采样率可以根据所使用的PC（ 例如，14.9帧/秒）的处理速度的开销照相机与对象之间的距离，以及改变。 </li><li>确保所有更改退出检测设置模块之前保存。 </li><li>转接口设备，它负责从输入装置转换记录，模拟事件（ 例如，红外光束的中断，运行车轮等的移动）到二上gital日志。 </li></ol></li><li>数据采集 注意：以下软件命令相关的定制地中海PC IV程序（“向导”），提供会话参数一步一步输入（ 如 ，10小时测试期间，鼠标ID，组分配等 ）。 <ol><li>将每个鼠标放到指定的箱子。 </li><li>通过同时按下“记录”按钮，同步视频和活动跟踪包。 </li><li>离开房间实验静静。 </li><li>当记录期满（ 例如 ，几个小时，天或数周），去除小鼠和他们回到自己的家乡笼。 </li><li>测量瓶的重量和节省数字媒体的所有数字录音（硬盘驱动器，便携式USB记忆棒，DVD）。 </li><li>原始数据传输到电子表格。 </li><li>保存MPG文件的罕见行为的行为（ 例如 ，刻板，发作），随后得分。 </li></ol></li></ol>

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开放获取出版这篇文章是由地中海Associates公司（圣奥尔本斯，VT）赞助。

在动物中的作用效果的检测主要依赖于研究者的能力来限制固有行为研究的可变性。因此，认真控制和减少潜在的困惑，可能减少行为数据的可靠性和可重复性是很重要的。同时，重要的是要认识到，没有测试反映行为的一个单结构域，神经功能的知识是强制性的，而这种行为是对外部压力非常敏感。如果上述公设被理解的，人们可以得出结论，综合行为分析应该包括测量的响应的时间过程，以及，涉及基本功能特征和范例该抽头成特定的行为方面。许多这些条件可以使用动作和行为的行为电脑评估一个丰富的家庭笼的环境中实现。 迄今为止，它已经emphasi捷思人类疾病的认股权证的其他注意事项的小鼠模型中，行为表型。这一概念是基于的前提是，官能稳态由内部和外部的压力中的疾病发病的挑战。虽然所有潜在的困惑不得通过引入自动化，家笼表型被消除，与不一致环境设置，运输胁迫，并反复操作的问题被最小化。这显著提高整个研究的一致性和精度;即使是小规模的减少可变性可以提高检测的诱导的早期疾病的影响。事实上，INBEST提供了大量的信息，这允许起病，动力学，以及的行为变化程度的更为准确评估，以及各种疾病诱发的行为缺陷之间的重要关系。可靠的视频跟踪取决于两个照明条件。首先，漫射光，需要在试验室，以防止文物从附近的反射物体。第二，高色对比度可通过选择适当的地板的颜色从受试者颜色尽可能不同而实现。在我们的实验室中，这是通过使用水浸灯监视白化小鼠时位于下方的INBEST盒和黑色地板托盘实现（白色或灰色的背景会如果检测色素的菌株是足够的）。对于INBEST的事件记录方面，当前的硬件设置（1短笛显卡采用了4路输入）限制了4盒每台PC可以同时使用。这是一个相当小的数目的盒，而更合适的建立将需要8个或甚至16笼，因而2个或4枚，分别。优选，INBEST可以连续使用超过24小时的家笼。这将允许动物充分，观察者对环境和建立稳定的，昼夜的行为模式，它可以在一个偏见地进行分析。为防止因停电，持续功率苏电脑数据丢失pply（或至少一个不间断电源）必须是安全的。最后，为了保证每日食物摄取的适当评估，但应注意的是，食物颗粒的尺寸应不超过在食品分配器（单个食物丸的推荐的大小为20毫克）的孔的大小。 它不被忽视然而，这种分析也应包括如何不同INBEST措施可以彼此交互。例如，花费更多的时间在运行车轮的小鼠都可能摄取更高量的食物和水，以满足他们的增加热量的需求。同样，小鼠摄入更多的蔗糖溶液可减少食物的摄入量。这些结果的解释可能进一步的性能普遍提高复杂随着时间的推移，特别是在关于摄食行为和跑步轮活动。鉴于其激励性，实验者也可以考虑到蔗糖溶液和T限制访问他跑轮，以抵消后的摄食效应和过度减肥的可能性，分别。然而，这些问题可能​​在一些菌株比其他人更重要，因为小鼠的不同菌株具有不同的行为轮廓。尽管对于许多上述的问题进行基线和实验评估的控制，实验者需要认识到，这些变量需要解释INBEST数据时加以考虑。与此同时，行为的某些方面不能研究在归属笼的环境中，因此需要用标准试验来完成的受试者的行为简档的组合。 内标准化计算机化的监测，而具有弹性的环境中似乎是在当代的行为分析的合理的下一步。这种非侵入性的，ethologically为基础的方法将允许研究人员观察行为反应的全部曲目在延长的时间周期。该oretically，这可以通过在一个“虚拟”的，丰富的环境非常相似的自然栖息地学习行为来实现。几个研究小组已经描述了支持小鼠表型的行为在他们的家笼22-25基于视觉跟踪工具，在二人组合26，27，或在大型社会团体28的范围内。高精确度和空间分辨率可通过在一组小鼠28的积分视频跟踪与微芯片技术用于同时且同步采集行为数据来实现。热成像相机检测热签名的能力可与可植入的微芯片或转发器相结合，以提供各小鼠（ 例如 ，体温，心脏/呼吸率）的相对位置和基本的生理功能。此外，先进的3D跟踪系统​​会产生更多的准确与定量识别行为的行为。为了反复运行VARI测试ETY，这样的系统应自动化，远程控制，和模块化。例如，空间记忆可以通过编程远端线索对LCD的墙壁外观，或呈现/隐藏掌柜从可移动地板可口的食物进行研究的大环境。以类似的方式，新的对象可以被呈现/隐藏在整个研究过程中的特定时间。这样计算机化表型可能有助于阐明的行为，致病机制基础疾病模型，以及新的治疗策略的开发的遗传决定因素。如果达到相对于测试条件，测试序列，以及所使用的硬件和软件的共识，可以预期，期待已久的标准化将提高行为研究的重现性，提升实验心理测量到一个新水平。

在基因工程，在过去的几十年中迅速的进步已导致人类疾病的动物模型的一个前所未有的增殖。小鼠获得了初级实验对象在生物医学科学的地位有几个原因。从实际的观点来看，它们具有高繁殖率，相对便宜，并且容易容纳。从概念的角度来看，它们在遗传上接近人类，可以遗传修饰相对容易，并有高度发达的内分泌，免疫系统和神经系统。除了 ​​病变在基因和细胞水平，脑功能障碍的现代研究需要复制功能缺损是高亮面，构造，或一种新的小鼠模型1的预测效度的示范。 在一个homoeothermic哺乳动物急性感染通常导致在发热反应，其与疾病的行为一起，构成了一个主要的生存机制2。急性病畜显示显著改变食物/饮水量和任务反光情绪反应，探索行为和学习/记忆能力的表现。这些变化主要是考虑影响了社会/性行为和保存能源的防御免疫反应。然而，当急性状况转慢性（如在许多免疫，内分泌和神经系统疾病看出），行为性能进一步恶化，由于各个器官，包括脑3的结构损坏。 人类和动物的神经变性疾病常常伴随有神经学和行为缺陷的星座。因此，在长期患病动物的行为学研究的主要目的是为了区分引起周边症状赤字中枢作用。然而，标准的行为任务的持续时间相对较短的限制收集离子的关于基本功能的措施，例如嗅觉，休息，睡眠，食物/水的摄入量，或癫痫性发作的信息。这些措施纳入改善行为的分析，并允许更好的诠释在活动苛刻的任务性能。 在病鼠行为表型的改进 在评估患病小鼠的行为轮廓的不足之处已被快速处理必要的电脑连续监测单独的居所小鼠。虽然不同的行为的电池可以设计4，5，下面列出的是已被成功地用于建立神经精神狼疮6的动物模型中的步骤。这种电池是在疾病（ 图1），两个亚慢性和慢性模型反复施加诸如轻度认知障碍和阿尔茨海默氏病7。经过一系列的神经系统测试8-10交流ustom制造装置中，设计为通过利用连续监测的多个行为输出在富集家笼状环境，以满足上述要求，可以使用。这种ethologically为基础的自发探索性活动和行为动机的评估提供了其他范例，如反思性学习和记忆的性能缺陷比较全面的了解。 <img alt="图1" src="/files/ftp_upload/51524/51524fig1.jpg" /> 纵向行为表型在我们实验室的图1的示意图。该行为电池设计从less-演变朝性较强压力的任务，这是重复在不同时间点，以评估持续的因素，例如疾病的进展的影响，药物治疗或免疫反应。黑暗P期间进行INBEST和个人测试HASE，往往超过10和2小时分别缩写 ：R -反射; BW - 平衡木行走试验。 RR - 旋转杆; OT - 嗅觉测试; SP - 蔗糖偏好测试; SD - 降压试验; NO - 新型对象测试;的 - 开放式现场测试; SAB - 自发交替行为; FS - 强迫游泳实验; MWM - 莫里斯水迷宫。 * -试验的各方面（ 例如 ，位置，上下文，颜色，形状），该需要在随后的试验中在整个实验过程中改变。 连续录像和行为的分析，在一个家庭笼般的环境，在2007年11首次报道，它集成与自身免疫的小鼠研究中使用的行为测试更复杂的自动化设备，在“测量行为”满足一年后已提交12。综合行为车站（INBEST， 图2A）是一个模块化系统，哪些C一个住所，计算机控制的光刺激的omprises两个光电管控制lickometers（一个用于水，一个用于感兴趣的溶液），一个自动食物分配器，一个计算机化的运行车轮，和一个数字化的攀爬网格。延迟，频率和特定行为的持续时间是使用定制软件检查。运动和探索性活动（ 例如 ，一个新的对象或陌生的同种的），可与视频跟踪软件（ 材料/设备清单 ）进行评估，睡觉时，减少频繁的行为模式，如自伤行为和癫痫发作，可用视频跟踪软件或专用事件记录包人工评分。 8个完整INBEST /视频设置被使用，从而允许并行的监测4个实验和4的对照动物（ 图2B）。 <img alt="图2" src="/files/ftp_upload/51524/51524fig2.jpg" /&gt; 图2.集成行为车站。（A）硬件设计的INBEST箱（L = 39×宽= 53×高= 50厘米）用示意图和软件。 （B）8个完整INBEST盒提供四个实验和四个对照组小鼠的并发家笼监测的机会。 <a href="https://www.jove.com/files/ftp_upload/51524/51524fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 因变量包括：食品/水的摄入量，响应的测量可口的刺激，自发的活动能力，登山，跑步自愿，焦虑相关的行为（ 如新物体的探测），美容，抓住和睡觉。此外，视觉刺激可以提交调理和学习的范例。 INBEST超过标准的行为测试的优点包括消除混杂影响INDUC由运输应力，以及反射夜行性活性，勘探，焦虑相关和抑郁样行为的措施连续化，自动化收集编敏感硬件组件与视频跟踪软件包的整合产生了大量的信息，这允许行为的改进评估有关的慢性疾病的进展在不同的动物模型。 INBEST可以用来研究其他慢性CNS疾病（ 例如 ，自闭症，严重抑郁症，精神分裂症），以及在纵向研究集中于神经发育，系统性/肿瘤性疾病的行为的影响，并且延长药物。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Power control interface operating package</td>
			<td>Med Associates Inc.</td>
			<td>MED-SYST-8</td>
			<td>Interface box and PCI card that manage all A/D data inputs and outputs</td>
		</tr>
		<tr>
			<td>Stimulus light</td>
			<td>Med Associates Inc.</td>
			<td>ENV-221M</td>
			<td>28 V DC, 100 mA, 2.5 cm diameter light (for presentation of a conditioned stimulus)</td>
		</tr>
		<tr>
			<td>Head entry detector</td>
			<td>Med Associates Inc.</td>
			<td>ENV-254-CB</td>
			<td>Permits head entry detection into the pellet receptacle</td>
		</tr>
		<tr>
			<td>Photobeam lickometer</td>
			<td>Med Associates Inc.</td>
			<td>ENV-351W</td>
			<td>Infrared sensor system for detecting beam interception by snout</td>
		</tr>
		<tr>
			<td>Food pellets</td>
			<td>Bio-Serv</td>
			<td>F0163</td>
			<td>Dustless precisions food pellets (20 mg rodent grain-based diet)</td>
		</tr>
		<tr>
			<td>Food dispenser</td>
			<td>Med Associates Inc.</td>
			<td>ENV-203-20</td>
			<td>Automated food dispensing system consisting of elevated plastic container and dispensing tube</td>
		</tr>
		<tr>
			<td>Food receptacle</td>
			<td>Med Associates Inc.</td>
			<td>ENV-303R2W</td>
			<td>Infrared sensitive base to signal when food pellet is dispensed or collected</td>
		</tr>
		<tr>
			<td>Climbing mesh</td>
			<td>Med Associates Inc.</td>
			<td>CT-Climbing mesh</td>
			<td>Durable metal rungs, dimensions</td>
		</tr>
		<tr>
			<td>Med PC IV software</td>
			<td>Med Associates Inc.</td>
			<td>SOF-735</td>
			<td>Integrates data acquisition from all electronic devices</td>
		</tr>
		<tr>
			<td>MPC2XL v1.4</td>
			<td>Med Associates Inc.</td>
			<td>SOF-731</td>
			<td>Raw data transfer utility</td>
		</tr>
		<tr>
			<td>Soft CR Pro v1.05</td>
			<td>Med Associates Inc.</td>
			<td>SOF-722</td>
			<td>Remote online monitoring software</td>
		</tr>
		<tr>
			<td>Running wheel</td>
			<td>Med Associates Inc.</td>
			<td>CT-MSUB-ENV-3042-X1</td>
			<td>Activity wheel for mice</td>
		</tr>
		<tr>
			<td>Digital counter</td>
			<td>Med Associates Inc.</td>
			<td>ESUB-ENV-3000</td>
			<td>LCD counter (4 counts = 1 revolution = 54.6 cm length)</td>
		</tr>
		<tr>
			<td>Picolo Diligent frame grabber</td>
			<td>Euresys</td>
			<td></td>
			<td>High-resolution PCI video capture card</td>
		</tr>
		<tr>
			<td>Ethovision XT 8.5</td>
			<td>Noldus Information Technology</td>
			<td></td>
			<td>Video-tracking software</td>
		</tr>
		<tr>
			<td>Camera</td>
			<td>Panasonic</td>
			<td>WV-BP334</td>
			<td>Digital, low-lux video camera suspended from a custom-made metal stand</td>
		</tr>
		<tr>
			<td>Video Splitter</td>
			<td>American Dynamics</td>
			<td>ADQUAD87</td>
			<td>Integrates and digitizes inputs from 4 video cameras</td>
		</tr>
	</tbody>
</table>

behavioral phenotyping of murine disease models with the integrated behavioral station (inbest)

由于基因工程的快速发展，小老鼠已成为生物医学研究的许多学科的首选对象。在慢性CNS疾病的研究，对于小鼠模型的需求日益增加的高效力在行为水平。然而，多个致病机制和复杂的功能缺损往往强加的挑战，以可靠地测量和解释慢性病患病小鼠的行为。因此，外周病理学和行为简档中的几个时间点用的试验电池的评估是必需的。视频跟踪，行为光谱和远程获取的生理措施的新兴技术，允许全面，准确，和公正的行为分析在家庭基状设置。这份报告描述了一个精致的表型的协议，其中包括一个特制的监控设备（集成行为车站，INBEST），专注于巴的长期测量SIC官能输出，如在相对压力的环境自发活动，食物/水的摄入量和动机的行为。在INBEST设计技术和概念的改进可以进一步促进重复性行为的研究和标准化。

图3例证不同的读奏的长期行为研究，CD1小鼠。数据代表基准性能（天6至2手术前），手术后的恢复（天2〜4），并诱导由脑反应性抗体的持续帧内脑脑室给药行为效应（天6至10;其中0表示在手术日）。分析事件的录音软件显示，实验组显示摄食行为障碍，就证明了水瓶舔（A）较低的频率，延迟增加接近蔗糖溶液（B），并在减少食品消费（C）实验期间。与这些变化相一致，它们也显示出减少的运行车轮的活性相比于对照小鼠（D）的。通过视频追踪软件测量，实验组也少走动在家里笼（E），并更愿意花更多的时间在住所（F）。这些行为差异再次说明样品ethograms（G）。 <img alt="图3" src="/files/ftp_upload/51524/51524fig3.jpg" /> 实验的小鼠的一系列10小时每日会话表示INBEST系统的判别功率图3代表的变量。（暴露于脑反应性抗体在2周）少饮水（A）中 ，需要较长时间才能接近蔗糖溶液（ B）中 ，并消耗在测试期间较少的食物（℃）。这些变化之际，他们也表现出受损的活动，例如为减少运行轮数（D），在住所（F）下跌行走（E）和长期逗留。这些行为的差异说明样品ethograms（G）。顶部面板显示的实验小鼠在第6天的行为，其特征在于降低的摄食行为，降低运行轮活动，相较于控制鼠标接收车辆（底部面板）增加庇护所的时间。 <a href="https://www.jove.com/files/ftp_upload/51524/51524fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

Watch this Scientific Journal Video about Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST at JoVE.com

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

在家庭笼的环境长期，全面的监测小鼠提供的脑部疾病的小鼠模型的异常行为有更深的了解。本文介绍了集成行为站（INBEST）当代行为分析的重要组成部分。

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 ...

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Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

9.8K 次观看.  McMaster University. 在家庭笼的环境长期，全面的监测小鼠提供的脑部疾病的小鼠模型的异常行为有更深的了解。本文介绍了集成行为站（INBEST）当代行为分析的重要组成部分。 

视频: Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

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 Assessment of the Aging Mouse Vestibular System

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.

Motor control and balance performance are known to deteriorate with age. This paper presents a number of standard noninvasive behavioral tests with the addition of a simple rotary stimulus to challenge the vestibular system and show changes in balance performance in a murine model of aging.

衰老小鼠前庭系统的行为评估

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of ...

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in different areas of their brain for the localization of their seizure focus and eloquent areas. After implantation, the patient must remain in the hospital until the pathological area of brain is found and possibly resected. During this time, these patients offer a unique opportunity to the research community because any number of behavioral paradigms can be performed to uncover the neural correlates that guide behavior. Here we present a method for recording brain activity from intracranial implants as subjects perform a behavioral task designed to assess decision-making and reward encoding. All electrophysiological data from the intracranial electrodes are recorded during the behavioral task, allowing for the examination of the many brain areas involved in a single function at time scales relevant to behavior. Moreover, and unlike animal studies, human patients can learn a wide variety of behavioral tasks quickly, allowing for the ability to perform more than one task in the same subject or for performing controls. Despite the many advantages of this technique for understanding human brain function, there are also methodological limitations that we discuss, including environmental factors, analgesic effects, time constraints and recordings from diseased tissue. This method may be easily implemented by any institution that performs intracranial assessments; providing the opportunity to directly examine human brain function during behavior.

Patients implanted with intracranial electrodes provide a unique opportunity to record neurological data from multiple areas of the brain while the patient performs behavioral tasks. Here, we present a method of recording from implanted patients that can be reproducible at other institutions with access to this patient population.

执行任务的行为与颅内电极主题

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in ...

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of current interventions to adequately treat fatigue in all patients leaves a need for new treatment options. Despite the therapeutic need and importance of preclinical research in helping identify promising novel treatments, few preclinical assays of fatigue are available. Moreover, the most common preclinical assay used to assess fatigue-like behavior, voluntary wheel running, is not suitable for use with some strains of mice, may not be sensitive to drugs that reduce fatigue, and has relatively low throughput. The current protocol describes a novel, non-voluntary preclinical assay of fatigue-like behavior, the treadmill fatigue test, and provides evidence of its efficacy in detecting fatigue-like behavior in mice treated with a chemotherapy drug known to cause fatigue in humans and fatigue-like behavior in animals. This assay may be a beneficial alternative to wheel running, as fatigue-like behavior and potential interventions can be assessed in a greater number of mice over a shorter time frame, thus permitting faster discovery of new therapeutic options.

Fatigue is a common, undertreated and frequently poorly-understood symptom in many diseases and disorders. New preclinical assays of fatigue may help to improve current understanding and future treatment of fatigue. To that end, the current protocol provides a novel means of measuring fatigue-like behavior in the mouse.

跑步机疲劳试验：疲劳类似的行为，为鼠标操作简单，高通量检测

Fatigue is a prominent symptom in many diseases and disorders and reduces quality of life for many people. The lack of clear pathogenesis and failure of ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

鼠类精神运动警觉测试（rPVT）：一个在大鼠和小鼠的神经行为评估性能的方法

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Basic Methods for the Study of Reproductive Ecology of Fish in Aquaria

Captive-rearing observations are valuable for revealing aspects of fish behavior and ecology when continuous field investigations are impossible. Here, a series of basic techniques are described to enable observations of the reproductive behavior of a wild-caught gobiid fish, as a model, kept in an aquarium. The method focuses on three steps: collection, transport, and observations of reproductive ecology of a substrate spawner. Essential aspects of live fish collection and transport are (1) preventing injury to the fish, and (2) careful acclimation to the aquarium. Preventing harm through injuries such as scratches or a sudden change of water pressure is imperative when collecting live fish, as any physical damage is likely to negatively affect the survival and later behavior of the fish. Careful acclimation to aquaria decreases the incidence death and mitigates the shock of transport. Observations during captive rearing include (1) the identification of individual fish and (2) monitoring spawned eggs without negative effects to the fish or eggs, thereby enabling detailed investigation of the study species' reproductive ecology. The subcutaneous injection of a visible implant elastomer (VIE) tag is a precise method for the subsequent identification of individual fish, and it can be used with a wide size range of fish, with minimal influence on their survival and behavior. If the study species is a substrate spawner that deposits adhesive eggs, an artificial nest site constructed from polyvinyl chloride (PVC) pipe with the addition of a removable waterproof sheet will facilitate counting and monitoring the eggs, lessening the investigator's influence on the nest-holding and egg-guarding behavior of the fish. Although this basic method entails techniques that are seldom mentioned in detail in research articles, they are fundamental for undertaking experiments that require the captive rearing of a wild fish.

A series of basic methods to enable the study of the reproductive ecology of fish kept in aquaria are described. These are useful protocols for collecting fish using SCUBA, transporting live fish, and observing the reproductive behavior of wild-caught fish kept in aquaria.

鱼类生殖生态学研究的基本方法

Captive-rearing observations are valuable for revealing aspects of fish behavior and ecology when continuous field investigations are impossible. Here, a ...

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer's Disease, Using IntelliCage

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive decline, such as Alzheimer&#39;s disease (AD), have become a promising tool to elucidate the underlying mechanisms and promote the therapeutic advances. An important step is the validation and characterization of expected behavioral abnormality in the models, in the case of AD, cognitive decline. The long-term behavioral investigations of laboratory animals to study the effect of aging demand substantial efforts from researchers. The IntelliCage system is a high-throughput and cost-effective test battery for mice that eliminates the need for daily human handling. Here, we describe how the system is utilized in the long-term phenotyping of a genetic Alzheimer&#39;s disease model, specifically focusing on the cognitive functions. The experiment employs repeated battery of tests that assess spatial learning and executive functions. This cost-effective age-dependent phenotyping allows us to identify the transient and/or permanent effects of genes on various cognitive aspects.

Automated, Long-term Behavioral Assay for Cognitive Functions in Multiple Genetic Models of Alzheimer&#039;s Disease, Using IntelliCage

This paper describes a protocol for cognitive assessments for genetic models of the Alzheimer&#39;s disease using the IntelliCage system, which is a high throughput automated behavioral monitoring system with operant conditioning.

基于 IntelliCage 的阿尔茨海默病多基因模型认知功能的自动、长期行为检测

Multiple factors&#8212;such as aging and genes&#8212;are frequently associated with cognitive decline. Genetically modified mouse models of cognitive ...

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by many patients prompts the need to develop new therapeutic alternatives and to better understand the etiology of the disorder. Pre-clinical models with translational merits are rudimentary for this task. Here we present a protocol for the unpredictable chronic mild stress (UCMS) method in mice. In this protocol, adolescent mice are chronically exposed to interchanging unpredictable mild stressors. Resembling the pathogenesis of depression in humans, stress exposure during the sensitive period of mice adolescence instigates a depressive-like phenotype evident in adulthood. UCMS can be used for screenings of antidepressants on the variety of depressive-like behaviors and neuromolecular indices. Among the more prominent tests to assess depressive-like behavior in rodents is the sucrose preference test (SPT), which reflects anhedonia (core symptom of depression). The SPT will also be presented in this protocol. The ability of UCMS to induce anhedonia, instigate long-term behavioral deficits and enable reversal of these deficits via chronic (but not acute) treatment with antidepressants strengthens the protocol&#39;s validity compared to other animal protocols for inducing depressive-like behaviors.

Here we present the unpredictable chronic mild stress protocol in mice. This protocol induces a long-term depressive-like phenotype and enables to assess the efficacy of putative antidepressants in reversing the behavioral and neuromolecular depressive-like deficits.

诱导小鼠快感缺失的不可预测慢性轻度应力协议

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by ...

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and dementia. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to some Parkinson&#8217;s-like symptoms by destroying dopaminergic neurons in the substantia nigra of the brain. It has been thus used to establish PD models in various animal studies. Here, mice receive MPTP injections (20 mg/kg/day) for seven days and the behavioral tests are performed on the eighth day. This model is adapted efficiently in the study of PD. The behavioral tests here include the cylinder test and the open field test. The cylinder experiment is used to detect the animals&#8217; ability to lift their front paws when put into a different environment. As the PD model mice show arching&#8212;the mouse arches its back&#8212;the number of paw liftings decrease. This test is easy to execute. The open field test is used to detect the amount of time the mice spend on running, walking, and remaining immobile. We analyze animals&#8217; movements in open field using software and obtain data. Lastly, we use L-DOPA, one of the most commonly used PD drugs, as one example to show how to apply this model to the study of PD drugs. Our results indicate that MPTP neurotoxicity induces motor deficit which can be mitigated by L-DOPA.

Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson&#039;s Disease Model

We describe establishment of a murine model for Parkinson's disease using MPTP, and behavioral assessments using cylinder and open field tests to measure motor function. We then use L-DOPA as one example to show how to apply this model in the study of PD drugs.

小鼠 mptp 诱导的帕金森病模型中自发性运动的行为评估

Parkinson&#8217;s disease (PD) is a common neurodegenerative disorder disease, causing the phenomenon of shaking, rigidity, slowness of movement and ...

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.