The authors would like to acknowledge The Garnett Passe and Rodney Williams Memorial Foundation and the Bosch Institute Animal Behavioural Facility.

1。动物<ol><li>老鼠1岁，9，和13个月大的（C57/BL6）是从动物资源中心（澳大利亚珀斯）获得。这些小鼠被安置在标准的鼠笼博世啮齿动物设施在悉尼大学的12/12小时亮/暗周期，获得食物和水随意 。下面列出的程序已获悉尼动物伦理委员会的大学。 </li><li>把鼠标笼子进入考场每个测试10分钟前，让小鼠使其恢复到测试环境。 </li></ol> 2，转棒<ol><li>设置的旋转杆装置（ 图1A）： <ol><li>在旋转杆的每个车道安装销钉。 注意：在这种情况下大鼠销钉（70毫米直径）被用来代替鼠标的定位销（32毫米直径）从扒着木钉和执行“被动转”10阻止老鼠。 </li><li>断定离子对坐落在确保它们没有倾斜触摸旋转杆的地板和旋转杆的每个车道底部的导线磁登陆平台放在尽可能接近到每个车道的磁右侧壁不接触。 注意：在转棒测试的小鼠都必须走在向前的方向留在旋转和加速的定位销。当鼠标不再能够留在木钉，他们属于和取代的登陆平台，随后激活磁传感器。所花费的时间从旋转榫钉，在落下和行进的距离被自动计算每个小鼠，并在旋转杆的前部记录的显示屏幕上的时间的销钉转速下降。 </li><li> 2滑动的透明塑料板到每个转棒线的前方与底部的短板和长板上面。 </li><li>输入利用设在旋转杆的前键盘的测试参数。按照STEPS为2.1.4.1 2.1.4.6的加速旋转试验参数和步骤2.1.4.7至2.1.4.12的定速旋转试验参数。 <ol><li>设置测试的最长持续时间为60秒。 </li><li>设置要使用的车道数（或待测试的小鼠的数目）。 </li><li>设置测试，以5 RPM的启动速度。 </li><li>设置测试的最高速度至44转每分钟。 </li><li>设置测试，以60秒的升降温速度。 </li><li>置所选择的定位销的尺寸和旋转的大鼠销钉转动在向前方向的方向。 </li><li>设置测试240秒的最长期限。 </li><li>设置通道以用于1作为将小鼠单独测试的次数。 </li><li>设置测试的起始速度，以每分钟15转。 </li><li>设置测试的最高速度至15转每分钟。 </li><li>设置测试为0秒的升降温速度。 </li><li>选择的销的尺寸和旋转的方向设置成鼠销子转动以forwaRD方向。 注意：上面的设置可以被改变以适应不同的实验的需要。 </li></ol></li><li>放置一个摄像头在旋转杆的固定速度旋转试验前，让鼠标的审判过程中的行为可以被记录并用于以后的分析视频，以确定持续时间的小鼠能够留在转棒。 </li></ol></li><li>按照步骤2.2.1至2.2.4加速旋转试验： <ol><li>放置在每个固定销5分钟一个鼠标，让鼠标使其恢复到转棒。 </li><li>轻轻轻移小鼠面对旋转杆的背面，并开始旋转试验时，所有受试者都面临着这样的方向（参见图1B）。 </li><li>返回所有小鼠笼子里时，他们已经从旋转木棍倒下，让他们10分钟的休息与获取食物和水。 </li><li>重复步骤2.2.1至2.2.3完成共8项试验，确保清理销钉，车道，以及旋转杆的尿液和粪便的落地平台，移动登陆平台回悫每次试验的起始位置。 注意：第3-5试验是用来作为训练试验，让老鼠与任务熟悉。下跌的时间，行走距离和木钉在秋天以后每次审讯时结束转速被记录供以后分析（ 图2）。 </li></ol></li><li>按照步骤2.3.1到2.3.8的固定速度旋转试验： <ol><li>放置在销子5分钟1小鼠，以允许它以不变的旋转杆。返回鼠标回到它的笼子。 </li><li>启动视频录制的摄像头，然后按下开始在转棒上。然后将鼠标放在旋转销钉确保它所面临的旋转杆的后面。 </li><li>停止录像摄像机上，当鼠标落在从旋转的销钉，并用获取食物和水返回鼠标其笼10分钟。 </li><li>直到一共有8个试验是后天确保清洁销钉，车道，以及旋转杆的粪便和尿液的着陆平台上重复步骤2.3.2和2.3.3，并移动登陆平台，回到它的每个试验的起始位置。 </li><li>开关上的定制的旋转体在3 Hz，持续20秒，以允许小鼠以熟悉的声音。通过切断钻头20秒后停止旋转，然后将手放在传动轮的任一侧，以持续旋转过去的初始20秒停止。 注意：该旋转体本身由一种啮齿动物传动轮固定到钻头（ 图3A）的。在传动轮的中心是一个小室用网状盖子上鼠标放置（ 图3B）。在转子旋转时在绕垂直轴逆时针的方向。刺激的幅度是在与显示旋转的刺激范围从0.2至3赫兹是足够来产生先前的研究一致吃了VOR和录像机的反应4,11,12。 </li><li>把鼠标在腔室内于所述旋转体的中心，并更换盖子。 </li><li>开关上的转子在3 Hz，持续20秒的最低设置。启动旋转杆，在此期间，准备为即将到来的审判开始在相机上的视频录制。关掉钻头在20秒结束时，然后将手在传动轮的两侧向从纺纱停止。通过将它尽可能快地在转动销后立即重新测试鼠标的旋转杆。 </li><li>停止在相机上的视频录制，当鼠标落在从木钉和返回鼠标笼子里。 </li></ol></li><li>用温和的清洁剂/水混合物并清洗干净的塑料板的圆柱销钉，小巷和带时，所有小鼠经测试70％乙醇的旋转杆的金属落地平台。 </li></ol> 3，平衡木与前庭挑战<ol><li>成立了巴矛杆束装置作为看出，在图4A中 。 注：平衡木设备是改编自卡特等人描述的设备（2001）13。对于本试验中，老鼠从光束，这是52.5厘米高于地面的下端走路，位于60厘米以上的地面变暗目标框（13×22厘米，用5×6cm的出入口）（ 图4A ）。老鼠自然会去寻觅黑暗和保护目标框赞成外露的横梁，并进一步鼓励由稍微倾斜的漏洞来在向上方向14上运行他们的自然逃逸机制来遍历光束。梁本身的长度为1米，具有一个直径为14mm的圆形横截面。可以使用光束直径的量身定做的范围，它允许实验者来调整试验的敏感性或容纳较大的课题。在平衡梁的下端的白线表示起跑线上。另一条线一直绘制从一开始线60厘米处梁的高端指示终点（ 图4A）。 <ol><li>位置2个摄像头，一个在平衡木的两侧，在平衡木（ 图4B）的下端。 注意：这些摄像机的角度应能捕捉到平衡梁的整个长度上，并确保标平衡木上的起点和终点线都清晰可见。这些相机将被用于视频记录小鼠的行为，因为他们穿越平衡木，具有被用于以后的分析得到的视频。 </li><li>线用纸巾的目标框的楼层，以便能够方便地清洁尿液和粪便检测每只小鼠后，并将其放置在壳体的圆顶从目标箱内的受试者在家笼。 </li><li>将足够的泡沫或其他衬垫材料的凸起梁的下方，以保护掉下来的设备的任何科目。那年秋天的小鼠会立即回升，由实验呃并放置在目标方框内休息。 </li></ol></li><li>将一个鼠标在2分钟的目标框，使其成为熟悉这个环境。覆盖开口向球门箱用戴着手套的手，持续5秒，如果鼠标试图在这段时间来阻止这种行为走路到光束。 </li><li>通过将其放置在横梁上刚刚开放的目标框框，允许它走进球门箱培养鼠标。继续通过将其放置在横梁上逐渐远离球门箱培养鼠标直到鼠标能够从起跑线步行到没有援助和最小的犹豫目标框。离开鼠标休息，在目标中为每个运行后1分钟。 </li><li>开始测试鼠标的时候训练结束。 <ol><li>开始录像的摄像头。 </li><li>把鼠标在梁的起始行和等待它穿过束在目标框的方向。 </li><li>停止视频录制的CA当鼠标到达箱meras。 </li><li>离开鼠标休息，在目标框中，持续1分钟。去除可能已经在审判过程中，而等待已存入任何尿液或粪便。 </li><li>重复步骤3.4.1至3.4.4，直到一共有5试验已经完成。 </li></ol></li><li>开关上在3 Hz，持续20秒（如在固定的速度旋转试验），以允许将小鼠以熟悉的声音定制的旋转器。通过切断钻头20秒后停止旋转，然后将手在传动轮的两侧向从纺纱停止。 </li><li>把鼠标在腔室内于所述旋转体的中心，并更换盖子。 </li><li>开关上的转子在3 Hz，持续20秒的最低设置。在这段时间开始录像的摄像头，在准备即将到来的审判。关掉钻头在20秒结束时，然后将手放在传动轮的任一侧，以持续旋转过去的初始20秒停止。 Ŧ转拨鼠标平衡木开始尽可能快地等待，当鼠标穿过束到目标框。 </li><li>停止摄像机的视频录制，当鼠标到达目标方块，并返回鼠标笼子里。 </li><li>用70％乙醇清洗平衡梁装置和改变纸巾在目标框后每只小鼠进行了测试。 </li></ol>

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The authors declare they have no competing financial interests.

该议定书中的关键步骤以前的工作已经表明，它很容易训练过度小鼠同时在旋转杆和平衡梁装置和作为结果，获得准确的测量结果可以是具有挑战性15。例如，过度训练对转棒可导致在这两个驯化和试用期的小鼠故意跳下销钉，而过度训练平衡木上可能会导致更频繁的停车（探索行为），并在相反方向行驶（ 即对启动线）15。最终，过度训练可导致电机实...

我们的平衡感，也许是连最基本的运动活动，包括散步和车削中最容易被忽视但非常重要的组成部分之一。平衡是由很多因素，包括肌肉力量，运动协调和前庭功能的影响，并且它仅在前庭神经病变的存在或不正常的老化过程中，一个全功能的平衡系统的重要性理解。扰动前庭系统往往以眩晕或头晕及不平衡导致摔倒和受伤以后1的风险增加的经验有关。这是在老年人群跌倒的地方是2伤的主要原因之一尤为关键。 前庭功能检查通常是基于前庭反射，尤其是前庭眼（VOR）或前庭collic反射（录像机）。在VOR和录像机是必不可少的图像上的稳定头部和身体的动作分别在视网膜和头部位置。一般情况下，VOR测量需要的搜索线圈微创植入测量眼球运动或眼球运动3的视频跟踪。这是在小鼠由于老鼠的眼睛和检测瞳孔的视频分析3难度小自然充满挑战。作为替代方案，录像机已被用来测量头的稳定响应于身体的动作小鼠而不需要侵入性手术4。尽管如此，一些研究特别侧重于前庭系统是如何执行作为一个整体，更重要的是它的老化过程中是如何变化的。 评估的综合平衡性能简单，无创，我们修改两个常用的行为测试。该旋转杆，斜平衡木测试评估啮齿动物和在以前的研究中电机性能的不同方面已经用于测试电池获得一个完整的简介电机能力。这种能力可能受疾病或遗传修饰，并且还以与正常发育和老化5-7相关联的处理敏感。使用旋转杆早期的工作表明，在小鼠运动协调3个月8岁后下降。此外，老鼠显示出明显的平衡赤字的平衡木测试9年龄的增加。 本文描述了为了挑战前庭系统和年轻人和年纪较大的老鼠表征上的平衡性能的后续影响使用与前庭刺激相结合的旋转杆和平衡木测试。虽然描述的简单，无创的方法并非设计为外周前庭功能独立的措施，他们也提供了一个有用而简单的行为措施，在前庭处理的多个阶段的小鼠正常老化过程中，比较细胞和亚细胞的变化。

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="84">
			<td height="84" style="height:84px;width:216px;">Rotarod</td>
			<td style="width:71px;">IITC Life Science Inc.</td>
			<td style="width:119px;">#755</td>
			<td style="width:167px;">&#34;Rat dowels&#34; = 70 mm diameter. Do not allow ethanol contact perspex.</td>
		</tr>
		<tr height="147">
			<td height="147" style="height:147px;width:216px;">iPhone</td>
			<td style="width:71px;">Apple</td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Can use any type of camera (e.g. Logitech webcam described above). Velcro fixed to the back surface for attachment to the the 3D articulated arm.</td>
		</tr>
		<tr height="126">
			<td height="126" style="height:126px;width:216px;">3D articulated arm</td>
			<td style="width:71px;">Fisso/Baitella</td>
			<td style="width:119px;">Classic 3300-28</td>
			<td style="width:167px;">Any type of stable vertical stand would be adequate. Velcro is fixed to the apical end of the arm for iPhone attachment.</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Wooden walking beam: 1m long strip of smooth wood with a circular cross-section of 14 mm diameter</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">A range of diameters and cross section shapes can be used to suit experimental parameters</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Wooden goal box (130 x 140 x 220 mm) made from 11 mm thick boards</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="378">
			<td height="378" style="height:378px;width:216px;">Support stand made of 41 x 41 mm beams: 2 vertical beams 525 and 590 mm from ground at the start and goal ends respectively; 803 mm horizontal beam that runs along the ground directly under the walking beam; two 20 mm long beams act as &#34;feet&#34;, joining the horizontal and vertical beams at each end; a 21 x 21 x 36 mm block hewn at the apical end of the &#34;starting&#34; vertical beam; a 13 x 13 mm aperture cut out of the centre of this block, forming a tunnel which runs perpendicular to the walking beam.&#160;</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Brace all joins with small steel brackets.&#160;</td>
		</tr>
		<tr height="147">
			<td height="147" style="height:147px;width:216px;">Adjustible metal ring (13 mm wide)</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Pass this through the aperture in the block, pass the starting end of the balance beam through this ring and tighten until the beam is firmly in place.</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">Black paint (water based)</td>
			<td style="width:71px;">Handycan</td>
			<td style="width:119px;">Acrylic Matt Black</td>
			<td style="width:167px;">2-3 coats for all wooden surfaces of the balance beam apparatus</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Clear finish</td>
			<td style="width:71px;">Wattle Estapol</td>
			<td style="width:119px;">Polyurethane Matt</td>
			<td style="width:167px;">Single coat for all beams. Double coat for all other surfaces of the balance beam apparatus</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Foam, packaging material</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">To cushion any falls from the balance beam</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Electrical tape</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Fix webcam to roof.</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:216px;">70% Ethanol, paper towels</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">Clean beam and goal box between each animal.</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Gauze pads/paper towels</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">To line the floor of the goal box</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Mouse house (from home cage)</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;"></td>
		</tr>
	</tbody>
</table>

behavioral assessment of the aging mouse vestibular system

在平衡性能与年龄有关的下降与不断恶化的肌肉力量，运动协调和前庭功能相关联。虽然一些研究显示变化的平衡表现型与年龄在啮齿类动物中，只有极少数孤立前庭贡献下正常情况下或在衰老期间的平衡。我们用两个标准行为测试在规定的年龄分以上的寿命来表征小鼠的平衡性能：旋转试验和斜平衡木测试。重要的是，一个定制的旋转体也被用来刺激小鼠的前庭系统（而不诱发运动病明显的迹象）。这两个测试已经被用来表明改变前庭介导的平衡性能是目前在鼠的寿命。初步的结果表明，无论是旋转试验和改性平衡木测试可用于老化作为替代更diffic期间识别变化的平衡性能ULT和侵入性技术，如前庭眼（VOR）的测量。

转棒小鼠的运动性能被描述为记录每只小鼠在8试验的时间要下降（TTF）。使用TTF的这些测量结果，对每个小鼠训练曲线可以绘制。 图2示出的酮1个月大的小鼠和1个9个月大的小鼠在8试验的过程中，电动机的性能的例子。这些训练曲线表明在第一个3-5的试验，随后再高原增加TTF。 TTF的测量结果记录在高原之前被认为是训练（ 图2），同时，形成了高原TTF?...

Watch this Scientific Journal Video about Behavioral Assessment of the Aging Mouse Vestibular System at JoVE.com

Behavioral Assessment of the Aging Mouse Vestibular System

电机控制和平衡性能是众所周知的恶化与年龄。本文介绍了一些非侵入性的标准行为测试与另外一个简单的旋转刺激衰老小鼠模型，以挑战在平衡性能前庭系统和显示的变化。

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 ...

behavioral-assessment-of-the-aging-mouse-vestibular-system

Research

JoVE Journal

Behavior

16.8K 次观看.  University of Sydney. 电机控制和平衡性能是众所周知的恶化与年龄。本文介绍了一些非侵入性的标准行为测试与另外一个简单的旋转刺激衰老小鼠模型，以挑战在平衡性能前庭系统和显示的变化。 

视频: Behavioral Assessment of the Aging Mouse Vestibular System

Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an entire gene expression pathway by inducing destruction and/or inhibiting translation of these targets. Several miRNAs play key roles in maintaining neuronal structure and function and in higher-level brain functions, and methods are sought for manipulating their levels for exploring these functions. Here, we present a direct in vivo method for examining the cognitive consequences of enforced miRNAs excess in mice by stereotactic injection of miRNA-encoding virus particles. Specifically, the current protocol involves injection into the hippocampal CA1 region, which contributes to mammalian memory consolidation, learning, and stress responses, and offers a convenient injection site. The coordinates are measured according to the mouse bregma and virus perfusion is digitally controlled and kept very slow. After injection, the surgery wound is sealed and the animals recover. Lentiviruses encoding silencers of the corresponding mRNA targets serve to implicate the specific miRNA/target interaction responsible for the observed effect, with na&iuml;ve mice, mice injected with saline and mice injected with "empty" lentivirus vectors as controls. One month post-injection, the animals are examined in the Morris Water Maze (MWM) for assessing their navigation learning and memory abilities. The MWM is a round tank filled with colored water with a small platform submerged 1 cm below the water surface. Steady visual cues around the tank allow for spatial navigation (sound and the earth's magnetic field may also assist the animals in navigating). Video camera monitoring enables measuring the route of swim and the time to find and amount the platform. The mouse is first taught that mounting the hidden platform offers an escape from the enforced swimming; it is then tested for using this escape and finally, the platform is removed and probe tests examine if the mouse remembers its previous location. Repeated tests over several consecutive days highlight improved performance of tested mice at shorter latencies to find and mount the platform, and as more direct routes to reach the platform or its location. Failure to show such improvement represents impaired learning and memory and/or anxiety, which may then be tested specifically (e.g. in the elevated plus maze). This approach enables validation of specific miRNAs and target transcripts in the studied cognitive and/or stress-related processes.

MicroRNAs have significant roles in brain structure and function. Here we describe a method to enforce hippocampal miRNA over-expression using stereotactic injection of an engineered miRNA-expressing lentivirus. This approach can serve as a relatively rapid way to assess the in vivo effects of over-expressed miRNAs in specific brain regions.

立体定向注射的microRNA表达慢病毒的小鼠海马CA1区和行为结果的评估

MicroRNAs (miRNAs) are small regulatory single-stranded RNA molecules around 22 nucleotides long that may each target numerous mRNA transcripts and dim an ...

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 ...

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models.

Mouse models have become increasingly popular in studies of behavioral neuroscience. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. This protocol describes the Pasta Matrix Reaching Task, which is a skilled motor task for use in mouse models of stroke.

补偿肢使用和运动技能学习行为评估以下感觉运动皮层损伤缺血性脑卒中的小鼠模型

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models ...

Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most common method for assessing exercise endurance in mice utilizes forced running on a motorized treadmill equipped with a shock grid. Animals who quit running are pushed by the moving treadmill belt onto a grid that delivers an electric foot shock; to escape the negative stimulus, the mice return to running on the belt. However, avoidance behavior and psychological stress due to use of a shock apparatus can interfere with quantitation of running endurance, as well as confound measurements of postexercise serum hormone and cytokine levels. Here, we demonstrate and validate a refined method to measure running endurance in na&#239;ve C57BL/6 laboratory mice on a motorized treadmill without utilizing a shock grid. When mice are preacclimated to the treadmill, they run voluntarily with gait speeds specific to each mouse. Use of the shock grid is replaced by gentle encouragement by a human operator using a tongue depressor, coupled with sensitivity to the voluntary willingness to run on the part of the mouse. Clear endpoints for quantifying running time-to-exhaustion for each mouse are defined and reflected in behavioral signs of exhaustion such as splayed posture and labored breathing. This method is a humane refinement which also decreases the confounding effects of stress on experimental parameters.

A method to assess exercise endurance in laboratory mice without the use of a shock grid is demonstrated. This method is a humane refinement that can decrease the confounding effects of stress on experimental parameters.

小鼠运动耐力的评估没有一个冲击电网的使用：另一种强迫运动

Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most ...

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the test mouse is placed in a standardized apparatus and relevant behaviors are assessed in three different sessions (called session I, II, and III).
The apparatus has three compartments (see Figure 1), the left and right compartments contain an inverted cup which can house a mouse (called &#34;stimulus mouse&#34;).
In session I, the test mouse is placed in the cage and its mobility is characterized by the number of transitions made between compartments. In session II, a stimulus mouse is placed under one of the inverted cups and the sociability of the test mouse is quantified by the amounts of time it spends near the cup containing the enclosed stimulus mouse vs. the empty inverted cup. In session III, the inverted cups are removed and both mice interact freely. The sociability of the test mouse in session III is quantified by the number of social approaches it makes toward the stimulus mouse and by the number of times it avoids a social approach by the stimulus mouse.
The automated evaluation of the movie detects the nose of the test mouse, which allows the determination of all described sociability measures in session I and II (in session III, approaches are identified automatically but classified manually). To find the nose, the image of an empty cage is digitally subtracted from each frame of the movie and the resulting image is binarized to identify the mouse pixels. The mouse tail is automatically removed and the two most distant points of the remaining mouse are determined; these are close to nose and base of tail. By analyzing the motion of the mouse and using continuity arguments, the nose is identified.
<img alt="Figure 1" src="/files/ftp_upload/52508/52508fig1.jpg" /> 
Figure 1. Assessment of Sociability During 3 sessions. Session I (top): Acclimation of test mouse to the cage. Session II (middle): Test mouse moving freely in the cage while the stimulus mouse is enclosed in an inverted cup. Session III (bottom): Both test mouse and stimulus mouse are allowed to move freely and interact with each other.

This protocol describes a method to quantify mouse sociability. Mice are videotaped as they move and interact in a special cage. Movie processing allows for the automated quantification of sociability with excellent accuracy and reliability.

使用自动图像处理方法鼠标社交性的实验评估

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the ...

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice

It is thought that rewarding experiences with drugs create strong contextual associations and encourage repeated intake. In turn, repeated exposures to drugs of abuse make lasting alterations in the brain function of vulnerable individuals, and these persistent alterations likely serve to maintain the maladaptive drug seeking and taking behaviors characteristic of addiction/dependence2. In rodents, reward experience and contextual associations are frequently measured using the conditioned place preference assay, or CPP, wherein preference for a previously drug-paired context is measured. Behavioral sensitization, on the other hand, is an increase in a drug-induced behavior that develops progressively over repeated exposures. Since sensitized behaviors can often be measured after several months of drug abstinence, depending on the dose and length of initial exposure, they are considered observable correlates of lasting drug-induced plasticity. Researchers have found these assays useful in determining the neurobiological substrates mediating aspects of addiction as well as assessing the potential of different interventions in disrupting these behaviors. This manuscript describes basic, effective protocols for mouse CPP and locomotor behavioral sensitization to cocaine.

This protocol is intended to enable researchers to conduct experiments designed to test these aspects of addiction using the conditioned place preference and locomotor behavioral sensitization assays.

可卡因诱导行为敏和小鼠位置偏爱评估

It is thought that rewarding experiences with drugs create strong contextual associations and encourage repeated intake. In turn, repeated exposures to ...

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 ...

Using the Race Model Inequality to Quantify Behavioral Multisensory Integration Effects

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) and humans reveal that intact multisensory integration is crucial for functioning in the real world, including both cognitive and physical activities. Much of the research conducted over the past several decades documents multisensory integration effects using diverse psychophysical, electrophysiological, and neuroimaging techniques. While its presence has been reported, the methods used to determine the magnitude of multisensory integration effects varies and typically faces much criticism. In what follows, limitations of previous behavioral studies are outlined and a step-by-step tutorial for calculating the magnitude of multisensory integration effects using robust probability models is provided.

The current study aims to provide a step-by-step tutorial for calculating the magnitude of multisensory integration effects in an effort to facilitate the production of translational research studies across diverse clinical populations.

使用种族模型不平等来量化行为多感官整合效应

Multisensory integration research investigates how the brain processes simultaneous sensory information. Research on animals (mainly cats and primates) ...

Using Unidirectional Rotations to Improve Vestibular System Asymmetry in Patients with Vestibular Dysfunction

The vestibular system provides information about head movement and mediates reflexes that contribute to balance control and gaze stabilization during daily activities. Vestibular sensors are located in the inner ear on both sides of the head and project to the vestibular nuclei in the brainstem. Vestibular dysfunction is often due to an asymmetry between input from the two sides. This results in asymmetrical neural inputs from the two ears, which can produce an illusion of rotation, manifested as vertigo. The vestibular system has an impressive capacity for compensation, which serves to rebalance how asymmetrical information from the sensory end organs on both sides is processed at the central level. To promote compensation, various rehabilitation programs are used in the clinic; however, they primarily use exercises that improve multisensory integration. Recently, visual-vestibular training has also been used to improve the vestibulo-ocular reflex (VOR) in animals with compensated unilateral lesions. Here, a new method is introduced for rebalancing the vestibular activity on both sides in human subjects. This method consists of five unidirectional rotations in the dark (peak velocity of 320&#176;/s) toward the weaker side. The efficacy of this method was shown in a sequential, double-blinded clinical trial in 16 patients with VOR asymmetry (measured by the directional preponderance in response to sinusoidal rotations). In most cases, VOR asymmetry decreased after a single session, reached normal values within the first two sessions in one week, and the effects lasted up to 6 weeks. The rebalancing effect is due to both an increase in VOR response from the weaker side and a decrease in response from the stronger side. The findings suggest that unidirectional rotation can be used as a supervised rehabilitation method to reduce VOR asymmetry in patients with longstanding vestibular dysfunction.

A new rehabilitation method is presented for rebalancing the vestibular system in patients with asymmetric responses, which consists of unidirectional rotations toward the weaker side. By directly modifying the vestibular pathway rather than enhancing the multisensory aspects of compensation, asymmetry can be normalized within 1-2 sessions and show lasting effects.

使用单向旋转改善前庭功能障碍患者的前庭系统不对称性

The vestibular system provides information about head movement and mediates reflexes that contribute to balance control and gaze stabilization during ...

Assessment of Memory Function in Pilocarpine-induced Epileptic Mice

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal model of epilepsy, we generated pilocarpine-treated chronic epileptic mice. We present a protocol for three different behavioral tests using these epileptic mice: novel object location (NL), novel object recognition (NO), and pattern separation (PS) tests to evaluate learning and memory for places, objects, and contexts, respectively. We explain how to set the behavioral apparatus and provide experimental procedures for the NL, NO, and PS tests following an open field test that measures the animals&#8217; basal locomotor activities. We also describe the technical advantages of the NL, NO, and PS tests with respect to other behavioral tests for assessing memory function in epileptic mice. Finally, we discuss possible causes and solutions for epileptic mice failing to make 30 s of good contact with the objects during the familiarization sessions, which is a critical step for successful memory tests. Thus, this protocol provides detailed information about how to assess epilepsy-associated memory impairments using mice. The NL, NO, and PS tests are simple, efficient assays that are appropriate for the evaluation of different kinds of memory in epileptic mice.

This article presents experimental procedures for assessing memory impairments in pilocarpine-induced epileptic mice. This protocol can be used to study the pathophysiologic mechanisms of epilepsy-associated cognitive decline, which is one of the most common comorbidities in epilepsy.

皮洛卡平诱导癫痫小鼠记忆功能评估

Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal ...

Methods Article

衰老小鼠前庭系统的行为评估