这项工作的经费由美国国立卫生研究院/ NINDS NS07722-01和加德纳家庭中心为帕金森氏病和运动障碍。

最理想的老鼠应该在他们的活跃周期（暗）测试。在我们的实验室中的老鼠都保持在反向光/暗周期，使我们能够方便地测试小鼠在他们活跃的时期（和我们）。测试开始进入黑暗的循环，直到至少一个小时。然而，它并不总是可能的调查，以维护一个单独的鼠标房间反向光周期。在这种情况下，所有这三个测试可在光周期，但请记住，，时间穿越在横梁上，在汽缸内，并接触和拆卸时间的步骤和后轮的数量可能会再进行测试时，在这段时间内。 下面描述的所有三个测试可以由一个实验者进行，但对于那些谁不为经验丰富的处理和工作与老鼠或几乎没有经验，测量小鼠行为，那么，可能需要额外实验者。在这种情况下，第二实验者可以协助具有挑战性的束测试小鼠在横梁上，而其他实验者记录的审讯或第二个实验者可以在去除粘合剂试验运行的计时器，而其他地方在口鼻部和地方在笼子里的鼠标贴纸。 1。具有挑战性的光束穿透过程<ol><li>在桌面上，或在一个鼠笼变化的站3清洁鼠笼反转。一线笼均匀，使他们能够支持梁（1米）的长度。 </li><li>从最广泛的最窄部分和顶部的倒的鼠笼组装梁的四个部分。 </li><li>将小鼠homecage计划测试在其侧面和上面的梁端，使最窄的梁端信息，到homecage。 </li><li>拿起第一个鼠标，它的尾巴的基础，并支持其后肢手掌。将鼠标在广角端的光束，放开它的尾巴和删除您的汉四。 </li><li>让鼠标嗅探和左右移动，才能成为更好的导向装置，如果鼠标转身轻轻地重定向到所需的方向。 </li><li>抬起homecage（即使它有，其cagemates）保持在相同的位置，在其一侧，并把它关闭测试鼠标。由于测试鼠标开始尝试进入homecage它移回使鼠标不进入，但向前迈进了一步。这一切的方式继续做下来的光束。年底允许鼠标进入homecage的。每只小鼠在笼子里做同样的程序。这是第一个“辅助”的审判。 </li><li>梁应彻底清洗笼之间用消毒动物保健或兽医人员提供。于一个笼子里，重要的是要清除之前的下一个鼠标运行的光束偏离任何尿液或粪便颗粒，因为这样会分散下一个鼠标。 </li><li>一旦所有已经通过一个辅助试验，然后在笼子里的老鼠再次拿起第一个鼠标，并把它在广角端的光束。如果需要的话，用你的手轻轻将鼠标定位在所需方向轻轻触摸它的背面鼓励它沿着梁的长度到它的homecage。如果鼠标停止嗅探或步行的光束偏离正确的鼠标用你的手，或把它捡起来，并将其放置在同一段路面走下。你的手鼠标的梁端附近的指导。你想尝试，并尽量减少鼠标停止探索，而在横梁上。越是这样做是在训练过程中，鼠标在测试过程中往往做。 </li><li>试用期结束时，将鼠标放在它的前肢到homecage中。然后下鼠标就可以收到第2次试验。小鼠共收到5次试验的第一个训练日，每个鼠标之间的交替，使小鼠试验间的间隔30秒以上。一般的做法是将遍历的最后几个试验老鼠的长度束，对自己，而不需要用于校正。 </li><li> 24小时后，第2天的培训，就可以开始。第2天的老鼠在同一束设置在1天的5个试验。老鼠不应该需要任何帮助，但可能需要加以纠正或感动的背面，以防止停止或探索。 </li><li>实际测试24小时后一天就可以开始。在测试当天，该光束被以类似的方式，以2天的培训。然而，现在的网格的网格，对应于每个波束宽度被放置在每个梁部分的顶部。 Â视讯摄影机是用来记录所有的光束穿透试验，可以由一个或多个实验者。 </li><li>标记卡信息（日期，小鼠，试验＃等）的基本实验。将这张卡在前面的摄像头，并记录为2-3秒，所以很显然正在测试鼠标，它是在什么样的审判。 </li><li>鼠标放置在顶部的网格表面上的最宽部分的光束，并录得这样沿束。该记录应该是足够接近，使鼠标的身体的整个长度上是可见的相机上。如果实在是太远了，那么单都很难看到，如果太靠近肢体运动可以错过。应该将摄像机定位，使得网格是在观看者的中间。 </li><li>在考试当天所有小鼠上获得5项试验电网浮出水面梁。 </li></ol> 2。梁视频分析<ol><li>可以直接观看视频从相机或连接到电视或电脑更大的屏幕视图。录像带应该拿下实验者盲基因型和治疗内的实验条件。 </li><li>每次试验的错误得分，因为视频播放慢动作。简或错误都算当鼠标正面临向前迈进。通过滑或外部的网格被认为是一个错误，当肢体滑倒超过0.5厘米以下的电网表面（半）。任何单鼠标停止后它的头转向一侧或定位不被视为错误。如果鼠标不能向前移动，肢体或四肢反复滑过电网，它是不是认为是一个错误。束后肢的基础上，在顶部的网格，并挂在一侧的脚趾上的狭窄段，这不被认为是一个错误。 </li><li>步骤也算在慢动作。的后肢面临的相机是用来跟踪的步数。开始计数，当鼠标使得其向前迈进的第一步，当鼠标放在它的前肢到homecage中结束。 </li><li>穿越时间用秒表得分，并实时完成。定时器开始当鼠标开始前进，结束时，第一前爪被放置在homecage时。 </li></ol> 3。气缸过程中的自发活动<ol><li>在桌面上，或在一个鼠笼变化的站3清洁鼠笼反转。安排两个笼子旁边到eACH〜18厘米的笼子，除了使前面临实验者。剩下的笼放在落后于其他两个笼子，将有助于支持镜像。 </li><li> 2笼顶部上放置一块玻璃，并将其定位，因此玻璃被得到的第2笼的外边缘。 </li><li>将活塞筒顶部的玻璃和玻璃下方的反射镜的角度，倚在第三保持架的背面。角度范围从30° - 45°，但更重要的是，鉴于从镜子中包括完整的气缸直径。 </li><li>视讯摄影机设置在镜子前调整镜子，视讯摄影机，直到你可以查看整个缸的底部直径。 </li><li>设置定时器3分钟，标签卡的重要实验的详细信息（日期，鼠标等）。 2-3秒videorecord标签。 </li><li>鼠标放置在缸，然后按记录和定时器。记录奥德鼠标三分钟。重要的是，试验区是安静，大声喧哗和谈话可以分散鼠标，可能会导致冻结行为。 </li><li>在3分钟，用一只手计数器的数量来计算的后轮，而在汽缸内，使鼠标。被定义为一个垂直运动，使鼠标仅在其后肢站立，两前肢离地板的后。在3分钟结束时，移开鼠标和将它放回homecage中。 </li><li>动物保健或兽医人员提供消毒剂清洁气缸和玻璃。允许的清洗液干燥前，在气缸内的下一个鼠标。 </li></ol> 4。自发活动分析<ol><li>可以直接观看视频从相机或连接到电视或电脑更大的屏幕视图。录影带应该拿下实验者盲基因型和治疗内的实验条件。 </li><li>前肢的步骤都算作视频慢动作回放。前肢步骤计数，当动物移动两个前肢在地板上的缸顺序连续运动。甲前肢运动是不计算在内，如果一个前肢，前肢的运动之间的时间长于5秒。后肢的步骤相同的方法，计算在前肢步骤。 </li><li>美容花费的时间用秒表测量和实时回放视频。计量美容吻，触须，身体上的较量。 </li></ol> 5。除粘<ol><li>将鼠标在考场或在一个鼠笼变化的站homecage。 </li><li>馈线斌从笼中取出和更换笼盖。允许鼠标/鼠标馈线1小时到考场，并在笼子里，而不习惯于。 </li><li>为了测试用干净的笼放置cagemates，所以测试鼠标是唯一一个在homecage。删除〜3/4的铺垫，并将其放置在干净的笼与cagemates。 </li><li>为了测试鼠标在homecage颈背和约束其使用到鼠标的鼻尖，一对小镊子地方之一不干胶标签。与镊子轻轻按下标签上的吻，然后松开鼠标。将上笼盖，并启动秒表。当鼠标使得其前爪记录时间试图移除标签。如果鼠标接触，但不会删除的标签，然后定时器保持下去，直到它并删除它，并记录时间，以及（接触和拆卸时间）。 </li><li>如果鼠标不接触或在60秒内撕掉，然后审判结束和贴纸被实验者手动删除。 </li><li>将测试鼠标在干净的笼子，并删除下鼠标，并将其放置在homecage并开始测试。所有小鼠获得3项试验。这是非常重要的小鼠之间交替，而不是做所有这三个试验鼠标在同一时间。试验的标签脱落或不固定在口鼻部不计算在内。 </li></ol>

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S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Restorative+effect+of+endurance+exercise+on+behavioral+deficits+in+the+chronic+mouse+model+of+Parkinson's+disease+with+severe+neurodegeneration.">Restorative effect of endurance exercise on behavioral deficits in the chronic mouse model of Parkinson's disease with severe neurodegeneration.</a> BMC Neuroscience. 10 (6), (2009).</li><li>Patki, G., Che, Y., Lau, Y. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mitochondrial+dysfunction+in+the+striatum+of+aged+chronic+mouse+model+of+Parkinson's+disease.">Mitochondrial dysfunction in the striatum of aged chronic mouse model of Parkinson's disease.</a> Frontiers in Aging Neuroscience. 1 (3), (2009).</li><li>Rommelfanger, K. S., Edwards, G. L., Freeman, K. G., Liles, L. C., Miller, G. W., Weinshenker, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Norepinephrine+loss+produces+more+profound+motor+deficits+than+MPTP+treatment+in+mice.">Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice.</a> Proceedings of the national academy of sciences of the United States of America. 104 (34), 13804-13809 (2007).</li><li>Li, Y., Liu, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mutant+LRRK2(R1441G)+BAC+transgenic+mice+recapitulate+cardinal+features+of+Parkinson's+disease.">Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease.</a> Nature Neuroscience. 12 (7), 826-828 (2009).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> What's Wrong With My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. , (2000).</li><li>Crawley, J. N., Paylor, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+proposed+test+battery+and+constellations+of+specific+behavioral+paradigms+to+investigate+the+behavioral+phenotypes+of+transgenic+and+knockout+mice.">A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice.</a> Hormones and Behavior. 31 (3), 197-211 (1997).</li><li>Fernagut, P. O., Chalon, S., Diguet, E., Guilloteau, D., Tison, F., Jaber, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+behaviour+deficits+and+their+histopathological+and+functional+correlates+in+the+nigrostriatal+system+of+dopamine+transporter+knockout+mice.">Motor behaviour deficits and their histopathological and functional correlates in the nigrostriatal system of dopamine transporter knockout mice.</a> Neuroscience. 116 (4), 1123-1130 (2003).</li></ol>

我们没有任何利益冲突。

在本研究中，我们将展示如何执行和分析三个有用的测试感觉功能的影响。这些措施包括具有挑战性的光束，在汽缸内的自发活动，和感官刺激（除粘）。选择这些测试是由于以下原因，1）我们和其他人发现他们是高度敏感基因小鼠模型14,16-18，2）黑质纹状体多巴胺功能障碍的不同程度，只需要很短的训练为梁和处理的感官刺激试验的反应，一旦训练检测可以执行在一个测试会话中，和3）来执行测试所需的设备的价格是相当低的相比，购买更自动化设备，如rotarod和开放场室。 具有挑战性的束流测试基因小鼠模型的PD检测电机的性能和协调赤字不仅是有用的，但也是有用的，我Ñ ​​发现损伤，在1 -甲基4 -苯基-1,2,3,6 -四氢吡啶治疗的6 -羟基多巴胺处理的小鼠和去甲肾上腺素的缺陷的小鼠19，23-25。此外，我们发现具有挑战性的光束按体重的影响较小，相比其他测试电机的性能及协调（rotarod和极点测试）。这是特别有益的工作时，中年雄性小鼠，体重可达50克。类似的光束，可靠地观察到自发活动改变帕金淘汰赛，PQ311X，THY1 ASYN，无晶体眼PITX3，LRRK2基因小鼠14，16-18，26。除粘测试也是敏感的遗传操作，包括帕金淘汰赛，帕金Q311X，THY1 ASYN，和DJ-1基因敲除突变小鼠14,16，17，22。于单侧的6 -羟基多巴胺处理的小鼠，它是如何典型的做法是用大鼠1,2类似的方式进行粘接剂的去除测试。不干胶标签被放置在每个前爪一个的镊子和时间删除标签被记录下来。我们发现6 hyrdoxydopamine治疗的小鼠不受影响肢体删除标签去除标签上患肢19日前。 该测试电池老化研究使用慢性治疗是很容易实现，但它也很容易使用药理研究。一旦动物是训练和准备测试一个测试站可以设置每个检测。然后，将动物以​​相同的顺序在每个测试运行。还可以施用的药物，一旦达到所需的药物峰浓度可以测试各小鼠在横梁上，然后移动到气缸三分钟，然后在粘接剂的去除试验。我们发现这种策略很好地工作时，测试不同的多巴胺受体激动剂在小鼠18，21。梁和去除粘合剂测试经得起反复测试，然而在汽缸内的自发活动受到反复作证纳克导致活动减少，随着时间的推移16。根据多么强大的赤字是在鼠标，您可能仍然能够检测到在气缸16的反复测试的差异。在一般情况下，习惯和减少活动，观察，尽快然而作为第二气缸接触，我们发现，我们可以得到足够的活动水平，当我们运行的自发活动试验紧随束穿越药理研究18,21。自发活动试验会话的数量，包括在一项研究中，将取决于对小鼠品系（有些是绝对比别人更积极）和治疗时间。在我们的药理研究小鼠混合C57BL / 6×DBA的背景下，我们测得2-4倍之间和测试会话活动，一个星期21分开。 束和汽缸测试要求测试后分析录象行为。有关这方面的分析特别重要的实验条件是盲目的评价者。当我们在实验室中培养新的评价者，我们前面所分析的由评价者专家从实验室的录像带的人得分的行为。解释和显示的标准，新的评价者，然后人开始自己得分先前分析的磁带。的分数，然后比较专家的评级。的人是不允许率的新数据，直到他们都在95-98％的精度的专家。然后，所有的数据都是随机抽查由专家评价者的准确性。 在这项研究中所描述的电池测试的目的是评估感觉功能的影响。但是，每当一个新的小鼠疾病模型的特征，它始终是重要的动物做了基本检查。应监测体重和温度在整个测试和任何异常行为，应当指出，像触须或cl去除asping的后肢时捞起的尾巴。基本神经系统评估的详细27-29。

帕金森病（PD）是一种使人衰弱的神经退行性疾病，主要特征是在黑质多巴胺能神经元逐渐丧失和路易体包裹体的发展在中央和周边系统。患者患有感觉障碍，包括运动迟缓，震颤，强直，姿势不稳，随着时间的推移而恶化。虽然罕见，导致家族性疾病，在过去15年中发现的潜在的疾病修改疗法的重要新目标的识别。突变基因编码的α-突触核蛋白，帕金，DJ-1，LRRK2，ATP13A2等等标志着一个新的“代”的PD动物模型，基因小鼠模型的发展。 优秀的非药物诱导行为的措施存在广泛的研究单方面6 - 羟多巴胺（6-OHDA）大鼠PD模型。这些测试包括肢体不对称，运动启动，躯体忽视，达到的能力，以及最近的超声波发声1-6。这些测试是不同程度的黑质-纹状体多巴胺神经元丢失的敏感，并已被广泛地用于各种类型的潜在疗法7-11评价疗效。然而，随着基因小鼠模型的最佳感觉测试使用或使用多少没有一个明确的共识。特征时，一种新的基因小鼠模型，在临床前研究，并试图使模型之间的比较时，这是有问题的。在过去的十年中，我们一直致力于电池已成功用于大鼠小鼠相似的感觉测试放在一起。在这篇文章中所描述的测试被用来帮助许多基因小鼠模型的PD的特点，目前用于临床前研究，测试新的潜在疗法12。 最常见的测试使用d来评估小鼠的运动功能活动的协调13在空旷的田野和旋转试验。虽然这些测试自动化，相对易于使用和感觉功能的信息，他们往往缺乏所需的灵敏度，在黑质纹状体多巴胺系统检测到细微的改变。例如，帕金缺陷小鼠与多巴胺功能的细微改变不显示小鼠在Rotarod障碍，但显示运动障碍，一个具有挑战性的束流测试14。此外，处理的小鼠与中等剂量的神经毒素1 - 甲基-4 - 苯基-1 -1,2,3,6 - 四氢吡啶（MPTP）不显示rotarod减值，但也有在一个倒置的步态和损伤的显着改变电网测试15。因此，只使用小鼠旋转表型评估的研究，可能会错过更微妙的障碍。理想的方法，在我们看来，行为特征是，包括学士学位ttery测试，敏感的感觉和运动功能的不同方面，和微妙的变化在基底节函数13-15。在这里，我们描述了如何衡量和分析感觉运动功能的小鼠使用一个具有挑战性的梁遍历测试，测试在汽缸内的自发活动，感官刺激测试和响应。

<table border="1">
 <tbody>
 <tr>
 <td>Material Name</td>
 <td>Company</td>
 <td>Dimensions</td>
 <td>Comments</td>
 </tr>
 <tr>
 <td>Challenging beam apparatus</td>
 <td>Starks Plastics</td>
 <td>Segment 1= 3.5 cm 
 Segment 2= 2.5 cm 
 Segment 3= 1.5 cm 
 Segment 4= 0.5 cm</td>
 <td>Contact information: 
 11276 Sebring Dr. 
 Forest Park ,OH 45240 USA 
Ph +1 (513) 541-4591 
 Fax +1 (513) 541-6773</td>
 </tr>
 <tr>
 <td>Cylinder</td>
 <td>Starks Plastics</td>
 <td>15.5 cm diameter 
 12.7 cm height</td>
 <td>Contact information: 
 11276 Sebring Dr. 
 Forest Park ,OH 45240 USA 
Ph +1 (513) 541-4591 
 Fax +1 (513) 541-6773</td>
 </tr>
 <tr>
 <td>Mesh Grid Wiring</td>
 <td>Ace Hardware</td>
 <td>1 cm2</td>
 <td></td>
 </tr>
 <tr>
 <td>Mouse Cages</td>
 <td>Ancare</td>
 <td>19 x 29 x 12.7 cm</td>
 <td></td>
 </tr>
 <tr>
 <td>Glass</td>
 <td>Ace Hardware</td>
 <td>19 cm2</td>
 <td></td>
 </tr>
 <tr>
 <td>Mirror</td>
 <td>Ace Hardware</td>
 <td>18 x 13 cm</td>
 <td></td>
 </tr>
 <tr>
 <td>Camcorder</td>
 <td>Sony HDR-HC9</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>MiniDV Tapes</td>
 <td>Sony DVC premium</td>
 <td>90 min long play</td>
 <td></td>
 </tr>
 <tr>
 <td>Labels</td>
 <td>AveryColor Coding Labels </td>
 <td>6.35 mm diameter (1/4" Round) </td>
 <td></td>
 </tr>
 </tbody>
 </table>

assessment of sensorimotor function in mouse models of parkinson's disease

敏感和可靠的行为结果的措施是必不可少的，以评估潜在的治疗许多神经退行性疾病的治疗在临床前试验中。在帕金森氏病，感觉测试敏感不同程度的黑质纹状体功能障碍的基本测试潜在疗法的疗效。可靠和相当优雅的感觉措施老鼠存在，但是很多这些测试测量感觉不对称大鼠内，不完全适用于新基因小鼠模型的PD。我们已经把灵感来自大鼠的敏感测试，适合老鼠的感觉测试的电池。在本研究中选择突出显示的试验电池在帕金森病小鼠模型的各种各样的，B a）在其灵敏度）便于在执行到一个研究，以及c）其低费用。这些测试已经证明有用的特性，以及在新的遗传帕金森病小鼠模型的试验锅差分疾病修饰疗法。

<p class="jove_content"具有挑战性的光束，在汽缸内的自发活动，除粘测试都是非常有用的分析，感觉功能的影响。我们已经找到了感觉功能的改变多个遗传和毒素的帕金森氏病的小鼠模型，包括帕金的淘汰赛，帕金Q311X，无晶体眼PITX3，α-突触核蛋白过表达，和单边6 - 羟小鼠中使用这些测试<sup&gt; 14，16-19</sup&gt;。在这里，我们展示收集的数据从小鼠体内过表达人野生型α-突触核蛋白在Thy1系子（THY1 ASYN）的和PITX3无晶体眼小鼠<sup&gt; 18,20</sup&gt;。在具有挑战性的光束，我们可靠地检测每一步的错误增加在Thy1系ASYN的比较野生型小鼠（<strong图1</strong&gt;）。在小鼠的同一行中，我们还多次检测后肢踩着强劲的减少在气缸（<strong&gt;图2</strong&gt;）<sup&gt; 12，16，21</sup&gt;。在去除粘合剂试验PITX3无晶体眼了深刻的黑质纹状体多巴胺神经元减少小鼠显示野生型对照相比显着增加的时间联系（<strong&gt;图3</strong&gt;）。</p&gt;<p class="jove_content" fo:keep-together.within-page="always"<img src="/files/ftp_upload/50303/50303fig1.jpg" alt="Figure 1"/<br /&gt;<strong&gt;图1。野生型组（n = 13）和THY1异步组（n = 4）在4个月的年龄，具有挑战性的错误​​。</strong&gt;<strong&gt; A）</strong&gt;每一步的错误，平均5个试验。<strong&gt; B）</strong&gt;平均每个波束宽度的错误。 **表示P &lt;0.01，分别比野生型小鼠。学生的t检验。</p&gt;<p class="jove_content" fo:keep-together.within-page="always"<img src="/files/ftp_upload/50303/50303fig2.jpg" alt="Figure 2"/<br /&gt;<strong&gt;图2。在气缸后肢踩着野生型组（n = 13）和THY1 ASYN的在4个月的年龄组（n = 4）小鼠。</strong&gt; *表示p &lt;0.05相对于野生型。学生的t检验。</p&gt;<p class="jove_content" fo:keep-together.within-page="always"<img src="/files/ftp_upload/50303/50303fig3.jpg" alt="Figure 3"/<br /&gt;<strong&gt;图3。联系时间在野生型组（n = 10）和PITX3无晶体眼组（n = 12）在4周龄的小鼠。</strong&gt; **表示p &lt;0.01野生型相比。采用Mann-Whitney U。</p&gt;<table border="1"&gt;<tbody&gt;<tr&gt;<td<strong&gt;测试</strong</td&gt;<td<strong&gt;参数</strong</td&gt;<td<strong分析选项</strong</td&gt;</tr&gt;<tr&gt;<td rowspan="3"<strong&gt;挑战束</strong</td&gt;<td&gt;错误</td&gt;<td rowspan="3"&gt;波束宽度（仅错误）<br /&gt;平均5次试验<br /&gt;个别试验</td&gt;</tr&gt;<tr&gt;<td&gt;时间</td&gt;</tr&gt;<tr&gt;<td&gt;步骤</td&gt;</tr&gt;<tr&gt;<td rowspan="4"<strong&gt;自发活动</strong</td&gt;<td&gt;前肢步骤</td&gt;<td rowspan="2"&gt;平均<br /&gt;前肢/后肢率的</td&gt;</tr&gt;<tr&gt;<td&gt;后肢步骤</td&gt;</tr&gt;<tr&gt;<td&gt;浅探</td&gt;<td&gt;平均</td&gt;</tr&gt;<tr&gt;<td&gt;美容时间</td&gt;<td&gt;平均</td&gt;</tr&gt;<tr&gt;<td rowspan="2"<strong&gt;除粘</strong</td&gt;<td&gt;联系时间</td&gt;<td rowspan="2"&gt;平均<br /&gt;中位数<br /&gt;最佳/最差分数<br /&gt;移走时间接触时间得分</td&gt;</tr&gt;<tr&gt;<td除去时间</td&gt;</tr&gt;</tbody&gt;</table&gt;<p class="jove_content"<strong&gt;表1。感觉运动功能测试电池：分析选项。</strong</p

Watch this Scientific Journal Video about Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease at JoVE.com

Assessment of Sensorimotor Function in Mouse Models of Parkinson&#039;s Disease

在帕金森氏病和运动障碍一般，敏感和可靠的行为分析是必不可少的，用于测试新的潜在疗法。在这里，我们描述了一个可管理的电池感觉敏感不同程度的损伤，黑质纹状体系统，并用于临床前研究的老鼠试验。

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  ...

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JoVE Journal

Behavior

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

54.7K 次观看.  University of Cincinnati. 在帕金森氏病和运动障碍一般，敏感和可靠的行为分析是必不可少的，用于测试新的潜在疗法。在这里，我们描述了一个可管理的电池感觉敏感不同程度的损伤，黑质纹状体系统，并用于临床前研究的老鼠试验。

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

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 ...

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 ...

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 ...

Community-based Adapted Tango Dancing for Individuals with Parkinson's Disease and Older Adults

Adapted tango dancing improves mobility and balance in older adults and additional populations with balance impairments. It is composed of very simple step elements. Adapted tango involves movement initiation and cessation, multi-directional perturbations, varied speeds and rhythms. Focus on foot placement, whole body coordination, and attention to partner, path of movement, and aesthetics likely underlie adapted tango&#8217;s demonstrated efficacy for improving mobility and balance. In this paper, we describe the methodology to disseminate the adapted tango teaching methods to dance instructor trainees and to implement the adapted tango by the trainees in the community for older adults and individuals with Parkinson&#8217;s Disease (PD). Efficacy in improving mobility (measured with the Timed Up and Go, Tandem stance, Berg Balance Scale, Gait Speed and 30 sec chair stand), safety and fidelity of the program is maximized through targeted instructor and volunteer training and a structured detailed syllabus outlining class practices and progression.

Community-based Adapted Tango Dancing for Individuals with Parkinson&#039;s Disease and Older Adults

Adapted tango has demonstrated efficacy for improving mobility and balance. We describe the dissemination of adapted tango teaching methods to dance instructor trainees and the implementation of adapted tango by the trainees in the community for improving mobility and balance in older adults and individuals with Parkinson&#8217;s disease.

以社区为基础改编的探戈舞的个人与帕金森氏病和老年人

Adapted tango dancing improves mobility and balance in older adults and additional populations with balance impairments. It is composed of very simple ...

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 ...

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 ...

Supramaximal Intensity Hypoxic Exercise and Vascular Function Assessment in Mice

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by international guidelines for patients suffering from cardiovascular diseases, more specifically, lower extremity artery diseases, where the patients' walking capacity is considerably altered, affecting their quality of life. 
Traditionally, both low continuous exercise and interval training have been used. Recently, supramaximal training has also been shown to improve athletes' performances via vascular adaptations, amongst other mechanisms. The combination of this type of training with hypoxia could bring an additional and/or synergic effect, which could be of interest for certain pathologies. Here, we describe how to perform supramaximal intensity training sessions in hypoxia on healthy mice at 150% of their maximal speed, using a motorized treadmill and a hypoxic box. We also show how to dissect the mouse in order to retrieve organs of interest, particularly the pulmonary artery, the abdominal aorta, and the iliac artery. Finally, we show how to perform ex vivo vascular function assessment on the retrieved vessels, using isometric tension studies.

High-intensity training in hypoxia is a protocol that has been proven to induce vascular adaptations potentially beneficial in some patients and to improve athletes&#39; repeated sprint ability. Here, we test the feasibility of training mice using that protocol and identify those vascular adaptations using ex vivo vascular function assessment.

小鼠低血压运动的下位强度及血管功能评估

Exercise training is an important strategy for maintaining health and preventing many chronic diseases. It is the first line of treatment recommended by ...

Dynamic Digital Biomarkers of Motor and Cognitive Function in Parkinson's Disease

As Parkinson&#8217;s disease (PD) is a heterogeneous disorder, personalized medicine is truly required to optimize care. In their current form, standard scores from paper and pencil symptom- measures traditionally used to track disease progression are too coarse (discrete) to capture the granularity of the clinical phenomena under consideration, in the face of tremendous symptom diversity. For this reason, sensors, wearables, and mobile devices are increasingly incorporated into PD research and routine care. These digital measures, while more precise, yield data that are less standardized and interpretable than traditional measures, and consequently, the two types of data remain largely siloed. Both of these issues present barriers to the broad clinical application of the field&#8217;s most precise assessment tools. This protocol addresses both problems. Using traditional tasks to measure cognition and motor control, we test the participant, while co-registering biophysical signals unobtrusively using wearables. We then integrate the scores from traditional paper-and-pencil methods with the digital data that we continuously register. We offer a new standardized data type and unifying statistical platform that enables the dynamic tracking of change in the person&#8217;s stochastic signatures under different conditions that probe different functional levels of neuromotor control, ranging from voluntary to autonomic. The protocol and standardized statistical framework offer dynamic digital biomarkers of physical and cognitive function in PD that correspond to validated clinical scales, while significantly improving their precision.&#160;

Dynamic Digital Biomarkers of Motor and Cognitive Function in Parkinson&#039;s Disease

This protocol offers a digitization of portions of traditional clinical tasks commonly used to measure cognition and motor control in Parkinson&#8217;s disease. Clinical tasks are digitized while biophysical rhythms are co-registered from different functional levels of the nervous systems, ranging from voluntary, spontaneous, automatic to autonomic.

帕金森病中运动与认知功能的动态数字生物标志物

As Parkinson&#8217;s disease (PD) is a heterogeneous disorder, personalized medicine is truly required to optimize care. In their current form, standard ...

Low-Cost Gait Analysis for Behavioral Phenotyping of Mouse Models of Neuromuscular Disease

Measurement of animal locomotion is a common behavioral tool used to describe the phenotype of a given disease, injury, or drug model. The low-cost method of gait analysis demonstrated here is a simple but effective measure of gait abnormalities in murine models. Footprints are analyzed by painting a mouse&#8217;s feet with non-toxic washable paint and allowing the subject to walk through a tunnel on a sheet of paper. The design of the testing tunnel takes advantage of natural mouse behavior and their affinity for small dark places. The stride length, stride width, and toe spread of each mouse is easily measured using a ruler and a pencil. This is a well-established and reliable method, and it generates several metrics that are analogous to digital systems. This approach is sensitive enough to detect changes in stride early in phenotype presentation, and due to its non-invasive approach, it allows for testing of groups across life-span or phenotypic presentation.

Footprint analysis is a low-cost alternative to digitized gait analysis programs for researchers quantifying movement abnormalities in mice. Because of its speed, simplicity, and longitudinal potential, it is ideal for behavioral phenotyping of mouse models.

神经肌肉疾病小鼠模型行为花型的低成本盖特分析

Measurement of animal locomotion is a common behavioral tool used to describe the phenotype of a given disease, injury, or drug model. The low-cost method ...