Kriss Franklin, Amanda Pollard and Justine Shaffer assisted in animal training and data collection. Sarah Freeman and Alisa Ivanova contributed to data analysis. This study is supported by WVU School of Medicine Start-Up, NIH/NIGMS U54GM104942, and NIH CoBRE P20GM109098.

下面的训练模式采用平均只SD大鼠相位调节的分析。请确保本文描述的协议是根据你的机构动物护理指南。在这项研究中的所有程序均按照机构的动物护理和使用委员会（IACUC）和Office实验室动物福利（OLAW）在西弗吉尼亚大学医学院的执行和使用实验遵循卫生准则的国家机构动物。 1.设备安装<ol><li>构建不对称的走道为开顶塑料盒中掺进了铝支持的每个角测量155厘米×104厘米（ 图1）。撑孔型两侧​​铝杆框的顶部边缘，以允许备用栓放置，沿盒的周边，以使每个连续的塞销上同一侧限定的步幅长度。 </li&gt; <li>放置20厘米×20厘米的平台上的每个角（共四个）分离表示的每边的条件。该距离应足以列入遍历由单个大鼠步骤周期的距离。 <ol><li>使用20厘米×1厘米×0.5厘米的尺寸由铝制钉。弯曲每个顶栓2.5厘米从尖端以产生足置台。 </li><li>固定钉使用滑动括号内经过加工的孔在同距离，以保证一级水平放置的开槽棒。调整用螺丝刀和一把尺子的位置。使用大约对应于平均大鼠爪尺寸1cm的栓宽度;较薄的或更宽的栓或者是不舒服或增加脚部放置变性。 </li></ol></li><li>操纵每侧塞销放置，以产生三个精确步进挑战条件之一。 <ol><li>通过将左我产生具有15厘米的步幅长度（SL15）的对称运动任务NTER-步幅长度（ 升 ISL）和右间步幅长度（R ISL）到步幅（7.5厘米）的一半。 </li><li>加上了另一对称条件（SL12）通过变更 L ISL 和 R ISL长度6.0公分。 </li><li>通过改变在左侧和右侧桩之间的距离产生的非对称的任务，被称为间步幅长度。向不对称地挑战电机系统，由20％改变升 ISL 并且 r ISL施加短间步幅长度无论是在左（L6R9条件）或右边（L9R6）侧。 1.5厘米扰动并处6厘米的升 ISL和9厘米řISL为L6R9条件，或为9cm的升 ISL和6厘米A R ISL为L9R6条件</li></ol></li><li>对于老鼠，保持步幅长度除SL12所有条件较佳15厘米。 </li><li>为方便起见，分配走道的每个长边的不对称条件利于在左侧或第r受试者的飞行侧，同时保留两个短边的对称控制条件。 </li><li>设置的高清晰度摄像机具有至少60赫兹的采样速率，使得四肢上栓的放置是通畅与相机指向垂直于带的视图覆盖约7步骤领域的走道。在靠近平台的第一和最后的步骤都被忽略。 </li></ol> 2.培训的设备<ol><li>请使用标准的培训资源， 例如 ，美国国立卫生研究院培训基本Biomethodology的实验室老鼠，到熟悉的啮齿动物的一般行为训练。 </li><li>在训练开始时，通过放置和奖励他们的20×20厘米的平台上进行至少5分钟适应受试者。然后，由食物奖励的呈现引导跨栓布置中，动物用1厘米间步幅长度到下一个平台。口头和抚摸的到达平台的奖励动物。 </li><li> AFTER 5训练运行，空间桩额外的1 - 2厘米外，进行下一个5训练运行。本文所列重复数是足以产生统计学适宜样本量（20 - 35步）。 <ol><li>如果动物获得的任务更慢作为判断步进（禁止停车）和姿势（弓背）的一致性，然后就大步恢复训练前集中培训，这些技能的加强在短步幅长度（S12）（ S15），最终接近所需的步幅。 </li><li>如果新的间距引起的焦虑或不适的任务，重新调整钉到以前的设置和重复训练模式。 </li><li>与此训练继续，直到合适的跨步幅长度达到四个条件和运动水平得到满足。根据我们的经验，老鼠声乐鼓励响应和线索开始一个试验。该测试可以在同一天进行的训练提供受试者被积极地执行任务。 注意:运动标准如下:散步是一致的，不涉及停止或失误;头部上下摆动是最小的;背面是拱形和运动过程中尾部升高;每个肢体显然从走道在发病的正交视图中可见和站立阶段的偏移。这个选择过程是必要的，因为目前的研究只是集中在散步，而不是其他gaiting行为。 </li></ol></li></ol> 3.测试和数据分析<ol><li>在S12，S15，L9R6和L6R9任务实验动物使用随机会话设计（1.3节所述）。利用休息时间，以避免在任务中的适应性。 </li><li>高清晰度摄像头，至少60赫兹的采样率记录会话。进口录像无需重新采样成视频编辑软件并只选择步行较量用于进一步分析。 </li><li>马克开始及运动相抵消从各学科录像。 </li><li>这里，使用定制软件称为videoa写入Matlab来手动识别姿态发病时间，并为每个肢体上一个帧接一帧的基础上，在那里姿态发病是由运动模糊的与肢体放置在相关的损失表示偏移一个栓钉，和姿态偏移，在肢剥离的发作发生，是由运动模糊的第一个证据指示。 </li><li>计算摆动阶段的持续时间为两个连续运动姿态起始点之间的剩余时间。排除任何行为与地上四脚行走并不一致， 例如 ，当步态蕴含着双重的摆动阶段（前肢后肢或掉在地上），从程序分析。 </li><li>绘制每个阶段的持续时间，为相应的步骤周期持续时间的函数。捕获与线性回归模型的关系（Tphase = B1 + B2 * Tc）的每个肢体，其中Tc为周期的持续时间得到，Tphase为either 碲伸肌相关姿态或Tf中，这是屈有关摆动，以及B1和B2是回归模型的经验常数（偏移和斜率）。 注意:斜率（B2）的表示变化的相持续时间的量，在运动的速度的变化。 </li><li>使用方程1和2（图2C），用于每个肢体来计算不对称性指数（AI）。两个方程具有一个简单的比率标准化两个值到它们的和的差值相同的形式。 <ol><li>使用等式1，计算出在水平差（ 艾高），使用姿态调制左（l）和右（r）的肢体的斜率之间的差。同样地，计算使用该斜坡从前面/前（a）和背面/后（p）的肢体的垂直不对称（AI v）中。施加这两个方程的结果是对应于1 4 的xy分）前肢不对称，数据集&lt;EM&gt; AAI H; 2）后肢不对称， 排 H; 3）左前肢，后肢不对称， 莱 伏; 4）右前肢，后肢的不对称性，RAI 诉 </li><li>绘制这些值作为贴剂（图2B）为不对称的跨所有四肢的可视化表示。 </li></ol></li><li>计算diagonality指数（DI），以评估一个前肢的参数和其对侧后肢（等式3中， 图2C）之间对角耦合。 </li><li>测试的DI，以及四个认可相对不对称条件之间的差| - |用于使用单向ANOVA与装置分析19事后比较统计学意义（ΔAI= AIL9R6 AIL6R9） </li></ol>

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The authors have nothing to disclose.

The rationale for this study was to develop a behavioral task that quantitatively assesses the changes in precise control of asymmetric locomotor behaviors. The existence of the spinal CPG has been functionally demonstrated for some time20, but the anatomical and functional characteristics that describe its mechanism as well as its modulatory inputs from descending or sensory feedback pathways have not been characterized until the past decade6,21,22. The current consensus is that the intrinsic spinal, sensory feedback, and descending commands are tightly integrated in the generation of locomotor behavior1
The asymmetric precise foot placement task presented herein is designed to functionally challenge the control systems responsible for the dexterous asymmetric control of stepping known to require cortical inputs23,24. This performance was assessed relative to the symmetric tasks that are less reliant on the descending cortical and brainstem control. Thus, we have an opportunity to discern the contributions of the spinal and descending pathways. Since the motor cortex is directly involved in the modulation of muscle phases during locomotion, reaching and postural adjustments9,10,25, the analysis of phase modulation in response to imposed asymmetric precise stepping tasks provides a basis for describing changes in volitional control. This is evident in the significant lateralized phase modulation between left- and right-favored tasks, characterized by the differences in asymmetry indices. We have also observed changes in whole body coordination that required diagonal coupling between contralateral forelimbs and hindlimbs, characterized by differences in the diagonal index.
Both focal stroke26,27 and spinal cord hemilesion28,29 animal models cause mild to moderate movement deficits akin to those observed clinically. In animal models, cortical lesioning of the corticospinal tract impedes or prevents precise stepping30,31. The application of our methodology to the characterization of cortical impairment in stroke models is yet to be described, though some of our preliminary data on rats with middle cerebral artery occlusions showed increased AI, and even a negative slope of the stance phase with increasing cycle duration for the limb on the side contralateral to stroke. This may correspond to a delay in the onset of consecutive locomotor phases, which is consistent with an asymmetry in both the step length ratio and the single limb support time observed in post-stroke patients15,32.
One limitation of this method is that it is inappropriate for the analysis of severely affected animals. However, this subgroup is not necessarily the focus of attention in studies of hemiparetic animals. Furthermore, subjective tracking of this type of deficit requires additional sub scales that may also be associated with high inter-rater variability, creating demand for gross computational methodology33. Thus, the challenge remains not in the assessment of deficits in the severely affected animals, but in the assessment of the mild to severe subgroup. Moreover, the ability to distinguish damage to specific hierarchical areas has been virtually impossible in a non-invasive method. The experimental setup presented herein is an effective tool for the evaluation of moderate impairment by monitoring modulatory activity of the motor antagonistic phases that drive the CPG with different speed demands, presumably contributed by higher order factors of the motor control hierarchy6.

在幸存的人群脑卒中发病率包括姿势在人类定量评价是一项挑战后的神经功能缺损1中风和动物模型粗大运动障碍。在临床上，这些运动障碍正在使用的主观标准，这是受到了广大患者表现出严重的，而不是中度受损更为敏感测量。同样地，伤后运动行为的动物，主观评价是常见的， 例如 ，在巴索，比蒂和布雷斯纳汉（BBB）运动尺度方法2,3。虽然这些主观评价方法帮助在四脚动物模型和人体步态康复研究之间翻译，与单独的肌肉群活性相关运动缺陷的细节没有评估。此外，要运动运动皮层贡献进行评估，为运动障碍的脑血管意外假定罪魁祸首，只能间接即便是使用最新颖的自动定量方法4,5得到，因为它们依赖于开放的领域或直线行走任务。这些任务不要求皮质贡献，并且可以由脊髓的神经机制， 即 ，中央模式发生器（CPG）网络，它可以幸免于神经损伤最动物模型，例如，spinalized动物6来执行- 8 。这些脊机制必不可少皮质贡献实验已经牵连于需要预期调整姿势9和达到10，以及精密的 ​​步进10的任务。 此外，大多数神经损伤是不对称的;例如，中风导致偏瘫， 即弱点在身上，这导致非对称步态11的一侧 - 。14。偏瘫步态的非对称性是由非对称spatiotempor产生人的肌肉激活伸肌相关立场相的缩短和步循环的屈相关摆动期的麻痹侧15,16拉长最显著表现。这种趋势还没有被开发在一系列运动的速度在健康或麻痹的动物。在目前的研究中，我们采用的相持续时间的特性17中的分析，它描述与循环的持续时间在每一步骤的函数的摆动或步态站立期的持续时间之间的关系。得到的线性回归模型，然后再与不对称的所有肢体进行分析说明。 我们报道了一种新的低成本的方法来评估下行皮质输入基于精确步进运动任务的四足动物的电机系统的活性。该任务的目的是通过规定徒步安置需求了行走速度的自然分布范围，挑战运动皮层。此外，脚放置要求被操纵到电机系统的左侧或右侧优先挑战。在一个类似的运动的任务，梅斯＆Whishaw（2009）研究了失败的速率，对不规则梯级走道错过的步数，在大鼠。我们的方法是免费的这个以前的研究，并详细相位控制的质量，"成功"的步骤 18。

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asymmetric walkway: a novel behavioral assay for studying asymmetric locomotion

行为分析通常用于感觉运动障碍的中枢神经系统（CNS）的评估。量化运动赤字在啮齿类动物中最复杂的方法是测量不受约束的步态地上分钟的干扰（ 例如 ，手动BBB评分或自动走秀）。然而，不要求用于由脊髓中央模式发生器（CPG）所产生的基本运动的产生皮质输入。因此，无约束行走任务测试运动障碍，由于运动皮质功能障碍只是间接的。在这项研究中，我们提出了一个新颖的，精确的脚的位置运动的任务，评估皮质输入到脊髓中央人民政府。一个仪表钉的方式来施加对称和非对称运动任务模仿偏侧运动障碍。我们表明，从转变在前肢姿态相位特性20％产生变化等距间步幅运动与PREF时错步长。此外，我们建议，非对称走道允许通过皮层控制信号产生行为结果的测量。这些措施是相关的减值皮质损伤后的评估。

图2示出了不对称的期间为一个单一代表受试者中运动任务的分析。分别计算的值使用公式1和2从所有受试者单独（图2）的所有条件，并从8雌性Sprague-Dawley大鼠复合数据（250 - 400克， 图3）。一般地，前肢站立阶段的调制是较小的，以该运动条件承蒙侧（短ISL），用的概念相一致，即在优选的侧（长ISL）步态站立期倾向于占据的较大部步骤周期相比偏爱的肢体作为运动速度减小。 从条件L9R6和L6R9（ΔAI）中得到相应的不对称指数之间的差异进行了测试用单向ANOVA（α= 0.05）和事后t-检验与conservativ<html>使用的anoval和multcompare功能在MatlabËBonferroni校正（调整α= 0.0125）。总体而言，组间差异有显著（P = 0.002）。对应于前肢之间的不对称的前部的水平非对称指数（AIΔAH）为左青睐（L6R9）之间显著差异（p = 0.006）和右青睐（L9R6）条件下（图4A）。为右侧垂直非对称指数（ΔRAI v）的条件之间的差异表现出的趋势，但它不是显著不同于零（p值= 0.031，α= 0.0125）。同样，我们发现了一个显著差异（p = 0.020，α= 0.05）的两个不对称条件下（ 图4B）之间的diagonality指数。方差分析检测发现在不同的任务DI间无显着差异，但只有一个单一的事后t检验，这不需要额外的阿尔法更正。 吨"FO:保持-together.within页="1"&gt;由于该方法依赖于解决非对称足放置动物的天然能力，一些动物可显示出疾驰样行为，其中双后肢分别同时在挥杆。此步态中观察到3只动物，和行为被排除进一步的分析。 <img alt="图1" src="/files/ftp_upload/52921/52921fig1.jpg" /> 图1.走道模型。用于对称和非对称步态任务人行道的（A）的示意图。（B）的穿心排列设置右 （R ISL）和左（ 升 ISL）相对于步幅长度（SL）间步幅长度。四个条件包括15厘米（SL15），对称的运动任务表示SL减少20％的步幅长度（SL）的一个对称的控制运动任务和优选的速度（SL12），左肢优选的（L9R6）和右肢体首选（L6R9）运动任务。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/52921/52921fig1large.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/52921/52921fig2.jpg" /> 图2.计算不对称与Diagonality指数。 （A）的姿态或摆动相持续时间（y轴）和循环持续时间（x轴），用于左肢青睐步态（L6R9）之间的关系由回归分析和数据点密度的热图被表示。相位特性派代表与利用斜截式支撑期线性回归。的插图对应于左前肢（LF），右前肢（RF），左后肢（LH）和右后肢（RH）下的热图。（B）的不对称指数所示计算等式（1）和（2），其中R，L，A和P -<html>在支撑期线性回归的斜率，如图（A）为左，右，前，后肢，分别丽 V，RAI V，AAI 小时 ， 排 H -左垂直，右垂直，前后，横向和后水平的不对称指数，分别计算出用于图1（C）的 Diagonality指数（DIS）中描述的所有四个条件计算如公式（3），用于在图1 的lF，RF， 左 ，右中描述的所有四个条件。 - 左前肢，前肢右，左后肢，右后肢站立期线性回归斜率。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/52921/52921fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> "&gt; <img alt="图3" src="/files/ftp_upload/52921/52921fig3.jpg" /> 图3.复合数据的不对称与Diagonality利用所有8个学科相位特性。 （A）热图表示立场的分配或摆动与周期持续时间为左肢青睐步态（L9R6）。站立阶段线性回归的相位特性被计算为图 1A，以及由斜截式插图表示。（B）的不对称指数计算为如图 1B所示。ΔlAIV，ΔrAIV，ΔaAI 小时并 ΔpAIħ -左竖右竖前-水平和后水平的不对称性指数的差异，分别减去相应asymm如等式3描述计算所有四个条件从屏幕左侧的青睐步态（L9R6）条件的权利，赞成步态（L6R9）的etry指数。星号-其计算采用自助法统计显着性<a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/52921/52921fig3large.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/52921/52921fig4.jpg" /> 非对称措施图4.分析。在条件L9R6及L6R9之间的不对称指数（AI）（A）。绝对差值进行了测试，单因素方差分析与事后t-检验分析与Bonferroni校正的多个测试调整。在L9R6和L6R9之间前肢不对称（ΔAAI h）上的变化是显著。条件diagonality指数（DI）的分布中的步骤S15，S12中，L9R6和L6R9使用单向方差分析（B）的分析用事后叔的测试不对称的任务（黑色）之间的区别。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/52921/52921fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

Watch this Scientific Journal Video about Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion at JoVE.com

Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

Here, we present a protocol to quantify precise stepping in rodents. Cortical and the spinal central pattern generator signals are required for precise foot-placement during obstructed locomotion. We report here the novel constrained walking task that directly examines precise stepping behavior.

非对称走道:一种新的行为检测方法的研究不对称步态

Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for ...

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8.7K 次观看.  West Virginia University School of Medicine. Here, we present a protocol to quantify precise stepping in rodents. Cortical and the spinal central pattern generator signals are required for precise foot-placement during obstructed locomotion. We report here the novel constrained walking task that directly examines precise stepping behavior.

视频: Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion

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 ...

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行为学

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

一个过程来观察大鼠巴甫洛夫空调酒精寻求行为的背景下引发的重建

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

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

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

执行任务的行为与颅内电极主题

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

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

联合穿梭盒子训练与电的Cortex记录和刺激作为一种工具来研究感知和学习

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

Novel Object Exploration as a Potential Assay for Higher Order Repetitive Behaviors in Mice

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals. RRBs are commonly split into lower-order and higher-order components, with lower order RRBs consisting of motor stereotypies and higher order RRBs consisting of perseverative and sequencing behaviors. Higher order RRBs are challenging to model in mice. Current assays for RRBs in mice focus primarily on the lower order components, making basic biomedical research into potential treatments or interventions for higher-order RRBs difficult. Here we describe a new assay, novel object exploration. This assay uses a basic open-field arena with four novel objects placed around the perimeter. The test mouse is allowed to freely explore the arena and the order in which the mouse investigates the novel objects is recorded. From these data, patterned sequences of exploration can be identified, as can the most preferred object for each mouse. The representative data shared here and past results using the novel object exploration assay illustrate that inbred mouse strains do demonstrate different behavior in this assay and that strains with elevated lower order RRBs also show elevated patterned behavior. As such, the novel object exploration assay appears to possess good face validity for higher order RRBs in humans and may be a valuable assay for future studies investigating novel therapeutics for ASD.

Higher order restricted, repetitive behaviors (RRBs) disrupt the lives of affected individuals. These behaviors are challenging to model in rodents, making basic biomedical research into potential treatments or interventions for RRBs difficult. Here we describe novel object exploration as a potential assay for higher order RRBs in mice.

新对象的探索在小鼠电位测定高阶重复的行为

Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals.  RRBs are ...

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

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

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

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

鼠类精神运动警觉测试（rPVT）:一个在大鼠和小鼠的神经行为评估性能的方法

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

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

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the animal&#39;s wellbeing and health. There are numerous behavioral tests that may be applied. We selected a test for general locomotion, the open field test (OFT); a test for muscular strength, the mesh test (MT); and a test for coordination, the rotarod test (RR). Testing can be accomplished on a weekly or monthly basis. As a test for general locomotion, the OFT works by objectively monitoring movement parameters while the mouse is in an open field apparatus. The field is generally a 2&#39; x 2&#39; box, and the movements are recorded through laser sensing or through video capture. The mouse is placed in the center of the open field and allowed to move freely for the test. The MT uses the latency for a mouse to fall off an inverted screen as a measure of muscular strength. A mouse is placed on a screen, which is inverted over a clear box, and is timed for their latency to fall. Three trials are performed, with the best of the three trials scored for that day. A score of 60 s is the maximum time a mouse is left inverted. Mice are given a 5-min rest period between mesh test trials. Lastly, an accelerated protocol on the RR assesses motor coordination and endurance. During a trial, a mouse walks on a rotating rod as it increases in speed from 4 rpm to 40 rpm over 5 min. The trial ends when the mouse touches the magnetized pressure sensor upon falling. Each mouse undergoes three trials, and the best trial is scored for that day. This combined behavioral data allows for the global assessment of mobility, coordination, strength, and movement of the test animals. At least two out of the three behavioral testing measures must show improvement for an animal to qualify as having overall improved motor function.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects of a disease or treatment on an animal's wellbeing. In order to globally assess motor functioning, we selected tests for general locomotion, muscular strength, and coordination: the open field test, the mesh test, and the rotarod test, respectively.

用于评估一般运动、肌肉力量和小鼠协调性的行为测试电池

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the ...

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal&#180;s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

A wireless, bidirectional system for multi-channel neural recordings and stimulation in freely behaving rats is introduced. The system is light and compact, thus having minimal impact on the animal&#180;s behavioral repertoire. Moreover, this bidirectional system provides a sophisticated tool to assess causal relationships between brain activation patterns and behavior.

用于体内的无线双向接口记录和刺激自由行为大鼠的神经活动

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...

A Behavioral Assay for Investigating the Role of Spatial Memory During Instinctive Defense in Mice

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often stereotyped actions elicited in response to innately aversive sensory stimuli, but their success requires enough flexibility for adapting to different spatial environments, which can change rapidly. Here, we describe a behavioral assay to evaluate the influence of learned spatial knowledge on defensive behaviors in mice. We have adapted the widely used Barnes maze spatial memory assay to investigate how mice navigate to a shelter during escape responses to innately aversive sensory stimuli in a novel environment, and how they adapt to acute changes in the environment. This new assay is an ethological paradigm that does not require training and exploits the natural exploration patterns and navigation strategies in mice. We propose that the set of protocols described here are a powerful means of studying goal-directed behaviors and stimulus-triggered navigation, which should be of interest to both the fields of instinctive behaviors and spatial memory.

This protocol describes a behavioral assay, based on the Barnes maze test, to study how instinctive defensive actions are modified by the knowledge of spatial environment.

一种研究空间记忆在小鼠本能防御中作用的行为分析法

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often ...

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.

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 ...