This work was supported by Interdisziplin&#228;res Zentrum f&#252;r Klinische Forschung (IZKF), University Clinics W&#252;rzburg, Germany (project N-215).

动物实验是由维尔茨堡大学和下弗兰肯行政区的法律国家机关按照动物保护准则和欧洲共同体委员会的指导方针（:55.2-2531.01十一分之七十六批准文号）批准。所有作出了努力，尽量减少使用动物的疼痛或不适。 注:18别处描述进行植入电极。 1.气缸试验（图2） <ol><li>通过用0.1％的醋酸溶液清洗筒准备一个透明的塑料玻璃圆筒（19厘米的高度:40厘米，直径）。 </li><li>与试验的日期和各组大鼠的识别号码准备卡。 </li><li>将两个镜子的背后汽缸90°角。 </li><li>将相机放置在圆筒的前部，使得照相机和气缸之间的距离允许爪子的良好视图。 </li><li>放置在运输箱的老鼠。 注意:动物应通过在测试之前，以避免应力实验者处理。 </li><li>从运家笼老鼠使用运输箱筒。 </li><li>放置老鼠的气缸（ 图3）英寸<ol><li>总是在一天的同一时间执行所有行为试验，以避免在活动的昼夜的差别。如果动物连接到由电缆的刺激发生器确保电缆在实验过程中不扭曲。 </li></ol></li><li>按下相机的"记录"按钮。显示用实验和大鼠的识别号码到摄像机的实际日期的卡。开始录制。 </li><li>五分钟后，取出从气缸动物，并把它放回使用运输箱的家笼。 </li><li>清洁用0.1％乙酸溶液中的圆柱体。 </li><li>通过计算左和右爪壁接触（百分比爪子使用），以及为r评估从记录的视频爪使用耳环（上后爪站在有或没有支撑在汽缸壁）。气缸试验也可通过适当的软件自动进行评价。 注:一个健康的老鼠同时使用爪子一样。帕金森病的老鼠使用的影响，由于病变程度较轻爪子。 </li></ol> 2.楼梯测试（图4） <ol><li>采集阶段<ol><li>训练的前一天熟悉的动物在楼梯测试中使用的颗粒。 <ol><li>可选:要增加动物的动机使用限制饮食（10-15 g标准的实验室食物的在自由摄食16级的90％，以保持体重）。然而，这不是强制性的，以实现正的训练效果。这项研究是没有食物限制进行。 </li></ol></li><li>制备透明塑料玻璃楼梯盒（高度34.5厘米，长35.5厘米，宽:12厘米和窄室6厘米）由清洁框用0.1％的交流客位酸溶液。注意:楼梯盒是一个两室盒与一个凸起的平台，并在狭窄隔室2楼梯。在狭窄的隔间楼梯左侧步骤只能与左爪到达，仅与右爪的正确步骤。 注意:标准梯箱包括两个隔室的盖子，如果它是用于实验经由电缆刺激大鼠，使用高盒子无盖。 </li><li>拆下楼梯，填补八个45毫克颗粒每一步井。 </li><li>将楼梯，并把另外八个小球高涨的平台上。 </li><li>放置在运输箱的老鼠。 </li><li>从运家笼老鼠使用运输箱楼梯框。 </li><li>放置在楼梯框大鼠（ 图5）。 </li><li>五分钟后，取出从楼梯盒子动物，并把它放回使用运输箱的家笼。 </li><li>注多少颗粒从平台和（最终）从右边和左边的楼梯食用。 </li><li>通过填写上有八个45毫克颗粒每一步井笔芯的楼梯。 </li><li>清洁用0.1％乙酸溶液中的楼梯框并将附加粒料在平台上。 </li><li>重复此过程（获取阶段），连续三天。 注意:所述的对雄性Sprague Dawley大鼠进行所有的实验。不同的培训模块的持续时间可以在不同的应变，性别和厂商的老鼠不同。 </li></ol></li><li>自由选择测试<ol><li>清洁用0.1％乙酸溶液中的楼梯框。 </li><li>拆下楼梯，填补八个45毫克颗粒每一步井。 </li><li>放置在运输箱的老鼠。 </li><li>从运家笼老鼠使用运输箱楼梯框。 </li><li>放置在楼梯框中的老鼠。 </li><li>五分钟后，从楼梯取出动物案例盒，把它放回使用运输箱的家笼。 注意:有多少小球从右侧和左侧的楼梯食用。 </li><li>注意:如果动物仍然有抓小球的问题，增加更多的一些平台，让他们可以很容易达成。 </li><li>通过填写上有八个45毫克颗粒每一步井笔芯的楼梯。 </li><li>与下一个动物0.1％的醋酸溶液清洗楼梯框。 </li><li>重复此过程（自由选择阶段）连续三天。 注:提供的结果是由无模块之间的休息时间进行训练获得。有些团体喜欢休息日进行整合，以支持训练过程。 </li></ol></li><li>强迫选择测试<ol><li>清洁用0.1％乙酸溶液中的楼梯框。 </li><li>除去楼梯和具有八个（模块前三天）或四个（连续THR填补左侧楼梯每个步骤的孔模块）45毫克颗粒EE天。 <ol><li>就在旁边，在那里将发生减值进行强制选择题。 注意:我们在右半球进行帕金森病变，因此选择培训左爪子。 </li></ol></li><li>放置在运输箱的老鼠。 </li><li>从运家笼老鼠使用运输箱楼梯框。 </li><li>放置在楼梯框中的老鼠。 </li><li>五分钟后，取出从楼梯盒子动物，并把它放回使用运输箱的家笼。 </li><li>注意有多少沉淀左楼梯吃掉。 </li><li>通过填写上有八个或四个45毫克的颗粒（颗粒的数量取决于训练日）的每一步井笔芯的楼梯。 </li><li>与下一个动物0.1％的醋酸溶液清洗楼梯框。 </li><li>重复此过程（迫选阶段）连续六天。 </li></ol></li><li>数据采集<ol> &lt;利&gt;作为用于强迫选择模块（在，每四个小球以及左侧楼梯）连续两天的说明来执行该实验。计算的成功率（吃掉粒料数目），为两天的平均值。 </li></ol></li></ol>

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The authors declare that they have no competing financial interests.

本文介绍了气缸和楼梯测试详细的培训方案。后者的目的是评估复杂抓行为和精细运动运动由于大鼠16,17熟练深远。结果测量被表示为试验，这是一种客观测量期间吃掉粒料数目。该协议可以在大鼠模型被用于帕金森病和其它运动疾病模型。气缸测试涉及一个简单的方法来评估大鼠爪子的使用。它无需培训，并且可以在一个高度标准化的方式从录像带被使用，由盲评价。我们选择有几个原因等等这些测试（开放的领域，单颗粒达到测试和步态分析）。这两个测试显示确实在我们的帕金森氏模型创建10爪子损害。它们是在结果相对坚固的测试结果可以在一个高度客观的方式来获得。这两项测试可以反复在SH使用ORT的时间间隔。在楼梯试验，在学习阶段沉淀把持增大并稳定在单个平台水平，所以到达高原后，它可以在不具有随着时间的推移16,20考虑依赖训练改进使用。 而钢瓶测试很容易申请，老鼠可以成为无聊和无效的。动物可以通过黑暗（执行与红灯测试），或在光暗周期后期的动机。后脚站起的测量是有助于监测对大鼠的正常活动。对于成功的楼梯训练，这是至关重要的过程中采集阶段激励动物。以确保该大鼠能够在第一把持方法抓住一些丸粒是很重要的。最直接的积极奖励导致在后期阶段良好的培训效果。当老鼠是不感兴趣的任务时发生的另一个关键步骤。在这种情况下，可能有必要施加温和食物限制，直到当达到适当的动机水平。 我们的研究设计的另一个重要问题是既定程序的一个很好的预测效度。原计划的设计，以被用作筛选平台为新颖刺激方案。虽然深部脑刺激是一种治疗选择不仅对帕金森氏病，也为震颤，抑郁症，强迫症，肌张力障碍等诸多条件，机制躺在其背后效力仍然知之甚少1,21。为了解决新颖，理性基于刺激方法要求有良好的动物模型。 更务实的态度迫使我们选择这可能是由通过电缆连接到刺激装置的动物执行的行为设置。汽缸是适当的用于此目的。市售的楼梯盒有盖子，因此，我们设计了原箱，这是较高的，并没有盖子的副本。这允许测试脑深部刺激过程中的表现。电缆驱动刺激的问题是在临床前研究常见。有一些设备能够刺激无需电缆，但它们的使用仍然有限22-24。对于我们的研究，我们必须设置不同的刺激模式，并进行长期的刺激。目前这只能通过电缆驱动的刺激，因为它允许不同的刺激特性的快速重新编程不接触动物来完成。在这方面，这项研究的设计是适合大多数研究组，电机结局脑深部刺激老鼠打交道。 总之，这份手稿提出了不同的实验DBS条件下，大鼠帕金森病研究成果电机全长协议。它描述了在楼梯盒子训练一个详细的协议，以及使用该圆筒试验的。所描述的训练方法相关的问题，可能会发生的不同，当大鼠应变，性别或厂商使用。大鼠根据自己的行为测试20,25,26的表现性和应变不同。在雌性大鼠发情周期也对他们的日常表现27产生影响。为了解决这个限制，雌性大鼠可容纳没有它的解同步发情周期28例。它也可以是必要的，根据在远系繁殖大鼠品系个体的学习曲线来调整训练阶段的持续时间。经常在行为测试中使用的食品限制应慎重使用。剥夺食物可能会增加动机，但另一方面降低抓20,29的精度。所描述的行为的电池，与帕金森病模型组合，可以用于研究不同的治疗方案和它们对电机结果的影响。对于丘脑底核脑深部刺激，这种研究设计具有较高的预测效度。

底丘脑核（STN）的脑深部刺激为帕金森氏病1和其他运动障碍的有效治疗选择。基本的机制仍然知之甚少和多因素的，但是一个重要特点是神经元网络活动通过在刺激电极2-4的附近轴突重复去极化调制。高频（&gt; 100赫兹）刺激，需要在大多数脑目标和DBS的最适应症的有益效果。从其他纤维，其通过刺激体积覆盖并且其中无意共激活深部脑刺激导致的副作用对...有用不同的功能，例如锥体束。因此，人们希望开发刺激参数，其中优先激活有益神经元素，同时避免副作用元件5,6的共激活。虽然神经生理学可以提供这种精细呕吐DBS的NG选项，科学发展在过去二十年中已经微乎其微，因为编程策略主要是被用在患者的"试错"评估和限用市售DBS设备有限编程选项，而不是使用神经生理学的洞察力并确定实验设置，系统地探索完整的参数空间。 为了克服DBS研究平移路障，我们提出了一个协议，在筛查临床探索之前帕金森的啮齿动物模型替代刺激参数。单方面帕金森氏大鼠疾病用6-羟多巴胺注射仿照到右内侧前脑束7,8。由此产生的病变，进一步描述为帕金森病，低剂量注射阿朴吗啡旋转后成绩评价阿朴吗啡试验进行评估和确认验尸由酪氨酸羟化酶immunohistochemistry。该方法是容易应用和高重现性的，而轴承的低死亡率和发病率。由此产生的运动障碍是非常离散7,8;这些动物都在自发的探索和把握复杂的行为表现出9,10对侧左爪子轻微受损。 评估的脑深部刺激协议测试需要其允许测量电机性能的快速和可靠的变化和可重复随着时间的推移与不同神经刺激的设置的有效性。一些研究小组已经提出了不同的激励方法和不同的测试，以评估在大鼠11高度可变和不一致的结果11-14的运动功能。这迫使我们选择了一套具有高测试预测效度和互补性。此外，对于脑深部刺激条件下，电机结果的评估，测试被看好这可以通过ANI进行MALS通过电缆连接到所述刺激发生器。为了这些目的，我们建立了我们的测试电池由一个测试用爪子不对称和对技术达到一个测试的。研究设计在图1中示出。 自发爪子使用我们执行通过Shallert 15，其是垂直勘探期间爪子使用广泛使用的测试中描述的气缸试验。动物没有训练是必需的。对于更复杂的抓行为的评估，我们根据蒙托亚16建立的楼梯测试。我们的协议是根据Kloth 17修改。将大鼠训练中从测试盒到达粒料一段十二天。训练期间后的试验可以应用于通过计数描述为食用粒料数目的成功率来测量复杂把持行为。本文介绍了在楼梯框中细致的培训，以及两者的性能BEH在天真，帕金森病和脑深部刺激条件avioral测试。

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a novel approach to assess motor outcome of deep brain stimulation effects in the hemiparkinsonian rat: staircase and cylinder test

底丘脑核的脑深部刺激为帕金森氏病的有效治疗选择。在我们的实验室，我们建立了一个协议，帕金森病（单侧损毁）大鼠筛选不同的神经刺激的模式。它包括通过在电缆结合外部神经刺激的24小时周期结束时注入6-羟基多巴胺（6-OHDA）入右内侧前脑束，植入慢性刺激电极插入底丘脑核和评估马达结果创建单方面帕金森病变。刺激用恒定电流刺激进行。的振幅低于副作用个体阈值为20％。马达结果评估是由气缸测试自发爪子使用的评估根据Shallert和熟练达到在根据蒙托亚楼梯测试评估完成。该协议中详细描述了楼梯框中训练中，Cylinder测试，以及在帕金森病大鼠同时使用的。使用两个测试是必要的，因为在楼梯测试似乎是精细运动技能障碍更敏感并且显示出更高的敏感性神经刺激期间改变。单方面帕金森模型和两个行为测试的组合允许不同的刺激参数的以标准化方式的评估。

所有动物都进行了多巴胺病变和电极位置的验尸组织学检验。只用在STN内正确的电极放置（ 图6）和完整多巴胺病变（&gt;在黑质多巴胺能神经元的90％的损失）动物被纳入结果部分（ 图7）。 损伤的条件下进行的圆柱体试验表明，损伤左爪子使用从约50％（天真的，健康的老鼠）减少到15.11％（平均）。根据以下24小时刺激期间定期130赫兹刺激（脉冲宽度60微秒），这是在帕金森氏症患者的标准协议，该爪子使用增加至21.9％（ 图8）。由于高的标准偏差这种差异在统计上并不显著。后脚站起次数未见differen假和刺激条件下，但此参数之间CES将包含在进一步研究，作为鼠的活动的测量。性能显然没有受到刺激电缆（ 图9）的干扰。 在我们的脑深部刺激研究中使用的所有的动物都能够学习颗粒十二天所描述的时限内到达。损毁前的平均成功率为13.5了28球（48.2％）的。损毁后的平均成功率显著降低至2.4粒料（8.6％）。它定期130赫兹的刺激在24小时的刺激时间（ 图10）的端部再次增加至7小球（25％）。的性能没有受到刺激电缆（ 图7）干扰。这两个电机试验在帕金森病大鼠评估运动障碍是互补的，并根据下默认therap改善了良好的预测效度<html> eutic条件。刺激电缆似乎对测试中的表现（ 图11）没有影响。 <img alt="图1" src="/files/ftp_upload/53951/53951fig1.jpg" /> 图1:。研究设计的单个步骤进行关于帕金森病大鼠不同的刺激方案的实验<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig1large.jpg" target="_blank">，请点击此处查看该图的放大版本。</a> <img alt="图2" src="/files/ftp_upload/53951/53951fig2.jpg" /> 图2:。缸测试设置安排镜子的圆筒盒<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 3"SRC ="/文件/ ftp_upload / 53951 / 53951fig3.jpg"/&gt; 图3:。气瓶检验气瓶检验过程中帕金森病大鼠<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图4" src="/files/ftp_upload/53951/53951fig4.jpg" /> 图4:楼梯测试设置布置成与上左楼梯粒料楼梯框。 （A）侧视图，从上面（B）查看。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图5" src="/files/ftp_upload/53951/53951fig5.jpg" /> 图5:楼梯楼梯测试试验过程中帕金森病鼠。<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig5large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图6" src="/files/ftp_upload/53951/53951fig6.jpg" /> 图6:。 刺激部位与黑色圆圈和植入手术过程中记录的相应尖峰信号指示右冠状动脉STN大鼠脑区（硫堇染色） <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig6large.jpg" target="_blank">点击此处查看该图的放大版本。</a> <img alt="图7" src="/files/ftp_upload/53951/53951fig7.jpg" /> 图 7:对酪氨酸羟化酶，多巴胺能神经元的标记物酶的6-OHDA损伤免疫组织化学的文档 。大鼠脑尾部的冠状动脉节呃单侧6-OHDA损伤。左健侧（LE）和损毁右侧（RI）的比较。在纹状体（a）和多巴胺能神经元在黑质多巴胺能纤维的单方面损失致密部（SNC），（c）所示 。比例尺= 100微米。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig7large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图8" src="/files/ftp_upload/53951/53951fig8.jpg" /> 图8: 爪子使用气缸试验圆柱体试验的结果表示为对侧（受影响由于病变）的百分比（100％ -同侧爪用[％]）爪子使用在各种条件下（损毁与130赫兹刺激）。 。数据被表示为平均值±SEM，N = 7， <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig8large.jpg" target="_blank">请</a><html>点击此处查看该图的放大版本。 <img alt="图9" src="/files/ftp_upload/53951/53951fig9.jpg" /> 图9:用电缆刺激的圆柱缸试验测试期间刺激帕金森病的老鼠。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig9large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图10" src="/files/ftp_upload/53951/53951fig10.jpg" /> 图10: 在楼梯测试成功率楼梯试验的结果表示为在各种条件（健康，损伤和130赫兹刺激）下抓握粒料数目。数据被表示为平均值±SEM，N = 7，P &lt;0.05（*）被认为是统计学显著（单向ANOVA + t检验）。3951 / 53951fig10large.jpg"目标="_空白"&gt;点击此处查看该图的放大版本。 <img alt="图11" src="/files/ftp_upload/53951/53951fig11.jpg" /> 图11:楼梯测试与刺激电缆楼梯测试期间刺激帕金森病的老鼠。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/53951/53951fig11large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

Watch this Scientific Journal Video about A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test at JoVE.com

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

一种新的方法，以评估在帕金森病大鼠脑深部电刺激效应的运动结果:楼梯和缸测试

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

a-novel-approach-to-assess-motor-outcome-deep-brain-stimulation

Nanyang Technological University

Research

JoVE Journal

Behavior

14.6K 次观看.  University Hospital Wuerzburg. Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

视频: A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

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

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal communication, and repetitive behaviors with restricted interest. As diagnosis is based on clinical criteria, any potentially relevant rodent models of this heterogeneous disorder should ideally recapitulate these diverse behavioral traits. The BTBR T+ Itpr3tf/J (BTBR) mouse is an established animal model of ASD, displaying repetitive behaviors such as increased grooming, as well as cognitive inflexibility. With respect to social interaction and interest, the juvenile play test has been employed in multiple rodent models of ASD. Here, we show that when BTBR mice are tested in a juvenile social interaction enclosure containing sawdust bedding, they display a repetitive synchronous digging motion. This repetitive motor behavior, referred to as &#34;inchworming,&#34; was named because of the stereotypic nature of the movements exhibited by the mice while moving horizontally across the floor. Inchworming mice must use their fore- and hind-limbs in synchrony to displace the bedding, performing a minimum of one inward and one outward motion. Although both BTBR and C56BL/6J (B6) mice exhibit this behavior, BTBR mice demonstrate a significantly higher duration and frequency of inchworming and a decreased latency to initiate inchworming when placed in a bedded enclosure. We conclude that this newly described behavior provides a measure of a repetitive motor stereotypy that can be easily measured in animal models of ASD.

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Inchworming is a highly repetitive synchronous digging motion displayed by BTBR T+ Itpr3tf/J (BTBR) mice when placed in a testing cage with sufficient sawdust bedding. The procedure is a modification of the juvenile social interaction protocol and is used here to assess repetitive motor stereotypies relevant to Autism Spectrum Disorder.

Inchworming:一种新型电机刻板的BTBR<em&gt; T<sup&gt; +</sup&gt; Itpr3<sup&gt; TF</sup</em自闭症&gt; /系小鼠模型

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal ...

Paw-Dragging: a Novel, Sensitive Analysis of the Mouse Cylinder Test

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore by rearing and touching the walls of the cylinder with their forelimb paws for postural support. Following ischemic injury to the forelimb sensorimotor cortex, rats rely more heavily on their unaffected forelimb paw for postural support resulting in fewer touches with their affected paw which is termed forelimb asymmetry. In contrast, focal ischemic damage in the mouse brain fails to result in comparable consistent deficits in forelimb asymmetry. While forelimb asymmetry deficits are infrequently observed, mice do demonstrate a novel behaviour post stroke termed &#8220;paw-dragging&#8221;. Paw-dragging is the tendency for a mouse to drag its affected paw along the cylinder wall rather than directly push off from the wall when dismounting from a rear to a four-legged stance. We have previously demonstrated that paw-dragging behaviour is highly sensitive to small cortical ischemic injuries to the forelimb motor cortex. Here we provide a detailed protocol for paw-dragging analysis. We define what a paw-drag is and demonstrate how to quantify paw-dragging behaviour. The cylinder test is a simple and inexpensive test to administer and does not require pre-training or food deprivation strategies. In using paw-dragging analysis with the cylinder test, it fills a niche for predicting cortical ischemic injuries such as photothrombosis and Endothelin-1 (ET-1)-induced ischemia &#8211; two models that are ever-increasing in popularity and produce smaller focal injuries than middle cerebral artery occlusion. Finally, measuring paw-dragging behaviour in the cylinder test will allow studies of functional recovery after cortical injury using a wide cohort of transgenic mouse strains where previous forelimb asymmetry analysis has failed to detect consistent deficits.

Classical forelimb asymmetry analysis of the cylinder test is routinely used to assess behavioural deficits in rats following brain injury or stroke; however, it fails to detect consistent deficits in mice. This study demonstrates that quantifying paw-dragging behaviour is a more sensitive analysis of brain injury in mice.

PAW-拖动:一本小说，鼠标缸试验敏感性分析

The cylinder test is routinely used to predict focal ischemic damage to the forelimb motor cortex in rodents. When placed in the cylinder, rodents explore ...

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

迷走神经刺激作为一种工具来诱导可塑性相关途径灭绝学习

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

一般方法评估对静脉注射甲基苯丙胺的自我管理深部脑刺激的影响

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing &#8220;in action and in context&#8221;. This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.

This protocol presents a novel methodology for the neural decoding of intent from freely-behaving infants during unscripted social interaction with an actor. Neural activity is acquired using non-invasive high-density active scalp electroencephalography (EEG). Kinematic data is collected with inertial measurement units and supplemented with synchronized video recording.

在自由，表现人类婴儿一种新的实验和分析方法意向的多模态神经解码期间社会互动

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental ...

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45&#176; to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

重复经颅磁刺激对大鼠大脑的单边半球

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, ...

Sit-to-stand-and-walk from 120% Knee Height: A Novel Approach to Assess Dynamic Postural Control Independent of Lead-limb

Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: STW). Thus, in clinical rehabilitation separation of sit-to-stand and gait initiation - termed sit-to-stand-and-walk (STSW) - is usual. However, a standardized STSW protocol with a clearly defined analytical approach suitable for pathological assessment has yet to be defined.
Hence, a goal-orientated protocol is defined that is suitable for healthy and compromised individuals by requiring the rising phase to be initiated from 120% knee height with a wide base of support independent of lead limb. Optical capture of three-dimensional (3D) segmental movement trajectories, and force platforms to yield two-dimensional (2D) center-of-pressure (COP) trajectories permit tracking of the horizontal distance between COP and whole-body-center-of-mass (BCOM), the decrease of which increases positional stability but is proposed to represent poor dynamic postural control.
BCOM-COP distance is expressed with and without normalization to subjects&#39; leg length. Whilst COP-BCOM distances vary through STSW, normalized data at the key movement events of seat-off and initial toe-off (TO1) during steps 1 and 2 have low intra and inter subject variability in 5 repeated trials performed by 10 young healthy individuals. Thus, comparing COP-BCOM distance at key events during performance of an STSW paradigm between patients with upper motor neuron injury, or other compromised patient groups, and normative data in young healthy individuals is a novel methodology for evaluation of dynamic postural stability.

Here, we present a novel protocol to measure positional stability at key events during the sit-to-stand-to-walk using the center-of-pressure to the whole-body-center-of-mass distance. This was derived from the force platform and three-dimensional motion-capture technology. The paradigm is reliable and can be utilized for the assessment of neurologically compromised individuals.

坐姿到站姿和步行距离120％膝盖高度:新方法来评估铅肢体的动态姿势控制独立

Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: ...

Behavioral Disturbances: An Innovative Approach to Monitor the Modulatory Effects of a Nutraceutical Diet

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, the traditional ways to monitor behavioral changes in dogs are complicated and not efficient. In the current clinical evaluation, a new, simple monitoring system was used to assess the effectiveness of a specific diet in positively modulating the intense and restless activity of 24 dogs of different ages and breeds. This protocol describes how to easily and rapidly evaluate improvement in a set of symptoms related to generalized anxiety by using a specific sensor, a mobile phone app, a wireless router, and a computer. The results showed that dogs treated with specific diets showed significant improvement in the times spent active and at rest after 10 days (p &lt; 0.01 and p &lt; 0.05, respectively). These dogs also showed an overall significant improvement in clinical and behavioral symptoms. A specific sensor, along with its related hardware, was demonstrated to successfully monitor behavioral changes relating to movement in dogs.

We report a simple approach to evaluate the effectiveness of a specific diet in positively modulating the daily activity and clinical and behavioral symptoms of dogs with evident behavioral disturbances.

行为障碍:一个创新的方法来监控保健品饮食的调节作用

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, ...

A Within-subjects Experimental Protocol to Assess the Effects of Social Input on Infant EEG

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants socially interact. Electroencephalography (EEG) power is an advantageous technique to assess infant functional neural activation. However, many studies record infant EEG only during one baseline condition. This protocol describes a paradigm that is designed to comprehensively assess infant EEG activity in both social and nonsocial contexts as well as tease apart how different types of social inputs differentially relate to infant EEG. The within-subjects paradigm includes four controlled conditions. In the nonsocial condition, infants view objects on computer screens. The joint attention condition involves an experimenter directing the infant's attention to pictures. The joint attention condition includes three types of social input: language, face-to-face interaction, and the presence of joint attention. Differences in infant EEG between the nonsocial and joint attention conditions could be due to any of these three types of input. Therefore, two additional conditions (one with language input while the experimenter is hidden behind a screen and one with face-to-face interaction) were included to assess the driving contextual factors in patterns of infant neural activation. Representative results demonstrate that infant EEG power varied by condition, both overall and differentially by brain region, supporting the functional nature of infant EEG power. This technique is advantageous in that it includes conditions that are clearly social or nonsocial and allows for examination of how specific types of social input relate to EEG power. This paradigm can be used to assess how individual differences in age, affect, socioeconomic status, and parent-infant interaction quality relate to the development of the social brain. Based on the demonstrated functional nature of infant EEG power, future studies should consider the role of EEG recording context and design conditions that are clearly social or nonsocial.

This novel protocol is designed to assess the neural bases of social interaction in infants. The paradigm is designed to tease apart how various social inputs such as language, joint attention, and face-to-face interaction relate to infant neural activation. Infant EEG power is recorded during both social and nonsocial conditions.

一个被试内实验协议，以评估对婴幼儿脑社会投入的影响

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants ...