这项工作是由美国国家科学基金会内部监督办公室1146334，美国国家科学基金会EFRI 0937848，DARPA N66001-10-C-2010，美国国家科学基金会和内部监督办公室0522220到RDB的支持。我们感谢斯塔西在君悦酒店普列斯顿公司公司在编制本稿件援助。

所有程序均按照布朗大学实验动物管理和使用委员会的指导方针。 1。系统概述视频跟踪系统与行为控制系统交互来监测在特定任务中的老鼠的工作进度，评估目标行为，控制刺激呈现和提供基于老鼠的进步奖励。体内的电生理记录系统收集的事件相关分析神经的数据。 （ 图1A）。 <ol><li>地板投影迷宫<ol><li>地板投影迷宫2是一个开放的领域没有围墙（147.3厘米×111.8厘米）用无色透明的树脂玻璃地板（0.9厘米厚）。地板的底面是一个单位增益双视觉面料屏幕使用的是短焦投影机伸过来的有机玻璃片第二个矩形（147.3厘米×111.8厘米×1.25厘米）背投。 </li><li>连接投影机在行为系统的PC视频卡。按住有机玻璃，屏幕面料，以及投影机采用阳极氧化铝框架。 </li><li>安装架空阳极框架安装架空摄像头和一个滑轮系统连接的ICS和探头系绳的老鼠。 注：连接框架保持地板投影迷宫和开销框架，以确保电气连续性和地面到前置放大器。 </li></ol></li><li>视频跟踪<ol><li>记录，跟踪和分析实时的视频与步骤1.2.2描述的单顶置摄像头。 </li><li>安装高架摄像头（标准VGA，80 FPS）到一个架空的阳极氧化铝框架来监控鼠</li><li>使用附连到老鼠的探头或者发光二极管（LED）来监测大鼠的位置，或与自动跟踪系统跟踪的大鼠的轮廓的形心。 </li><li>使用多厅影院的基本行为模块ONL分析位置数据国家统计局还保存数据文件，以便进一步离线分析。 注意：我们使用的电影院行为研究系统3.4.1的记录，跟踪和分析老鼠的位置。该影城跟踪模块用于跟踪老鼠。对动物的进展有效跟踪，使用国际影城基本行为模块在二维空间中具有的意义的任务的迷宫相关位置创建区域。区可以合并成序列，并CINEPLEX逻辑事件（如条目转换区和履行的序列）被分配，使得如果大鼠满足条件的事件，该事件为真。通过superport输入卡的行为系统分配具有数字输出和接口事件。 </li></ol></li><li>一个完全自动化的行为控制系统<ol><li>行为测试竞技场：使用适当的形试舞台上的地板投影迷宫行为的任务。构建有用NA磨砂白色亚克力，直接放置在地板上投影迷宫。 注 ：尺寸可根据客户的使用行为的任务。墙壁通常是45-50厘米的高度。这里我们使用双面测试领域（领结迷宫12），以最大限度地在一个会话（ 图1B的领结迷宫的尺寸）进行试验的次数。测试舞台拥有在追踪软件定义了四个指定区域：East图片区，西图片区，东审判准备好面积和西审判准备好面积（ 图1C）。 </li><li>行为系统：由MED-PC IV软件控制的行为接口系统运行内部编写的MEDstate符号的程序（见附录）。使用来自影城行为系统事件的任务期间跟踪老鼠的进度，控制图像呈现，提供声音提示，并提供奖励。 <ol><li>接口superport输出卡欧尼普莱克斯数字输入，收购时间STAMPED行为的事件发生在PlexControl软件环境进行离线分析。使用可编程音频发生器发出声音提示。 注：从这里展示的设备行为的事件可以根据需要通过数据传输板操作的第三方设备（ 如激光光遗传学刺激）。 </li><li>众议院superport输出卡，superport输入卡和可编程的音频发生器在桌面界面内阁。安装与使用安装在桌面内阁DIG-700F解码卡的个人计算机（PC）一DIG-704PCI-2 PCI接口卡。 </li><li>使用可编程颅内自我刺激刺激提供双极性方波ICS的老鼠。通过PHM152 COM卡的刺激器单元连接到PC。推荐ICS参数：脉冲1和2持续时间：500微秒;延迟脉冲1和2之间：500微秒;频率：100赫兹。 注：ICS交付任务过程中的自动化，但可以使用一个可编程的按钮盒接口与一个SmartCtrl模块可以手动交付。 </li></ol></li></ol></li><li>神经网络的数据采集系统<ol><li>保证地板投影迷宫框架和ICS系统接地到欧尼普莱克斯神经数据采集系统的前置放大器，以尽量减少在神经录音电噪声。 </li><li>同时收集神经的数据，从电影院和行为事件标志位置坐标从行为系统为离线数据文件中进行分析。 </li></ol></li></ol> 2。动物的制备<ol><li>动物<ol><li>取得天真22天岁男Long-Evans大鼠。 </li><li>对房子的老鼠，让他们逐渐适应了动物饲养一周。 </li><li>每天处理大鼠〜5分钟。 </li><li>一旦大鼠达到250-275克，开始食品日程维护他们的体重在他们的自由采食量85-90％。我们的目标ights都增加10克/个，直到大鼠达到350克</li><li>单家的老鼠和持续至少一个星期的食物时间表开始手术植入刺激和记录电极之前。 </li></ol></li><li>手术植入 开展在标准无菌条件，并根据制度和监管指引外科手术。 <ol><li>大鼠麻醉与异氟醚。 </li><li>做一个切口在头皮显露颅骨进行清洗和鉴定前囟和lambda的。 </li><li>做开颅手术的相关坐标。 </li><li>贴上骷髅锚螺丝。 </li><li>降低了ICS电极尖端进入MFB使用下列坐标：前 - 后，-2.7毫米的前囟门，侧，±1.8毫米，背腹，-8.5毫米的颅骨表面。第二ICS的电极可以被植入到对面半球中的情况下电极故障的备份。 </li><li>确保ICS电极到t他的头骨和锚螺丝骨水泥。不要在水泥基座电极（对刺激电极的塑料外壳）。 </li><li>记录电极降低到感兴趣的网站，并确保设备与骨水泥。 </li><li>定位在ICS座远离记录装置和固定在ICS电极和记录装置与骨水泥锚定螺栓。 </li><li>开始习惯到整形协议之前允许至少七天痊愈。 </li></ol></li></ol> 3。行为塑造：一般整形分为三个阶段：早期，中期，晚期整形（图2）。 注：初，中级整形的目的是培养大鼠维护每个试验中已准备好面积固定的“准备位置”，并在会议上进行大量的试验。半自动化的行为塑造这样的培训可以适应老鼠的个人学习率。 ONCEA老鼠是维持一个成功的“准备位置”，进行任务的具体整形（晚整形）与转让大鼠的目的到一个完全自动化的协议，用于精确和公正的行为控制（ 图2）。 <ol><li>初成形（ 图2A） <ol><li>第1天：习惯于大鼠的行为室温10分钟，用设备接通，然后返回到菌落。 </li><li>第2天：重复步骤1，然后习惯于动物的试验舞台10分钟。 </li><li>第3天：在ICS和探头连接臂连接到大鼠和习惯于大鼠的试验舞台10分钟。 </li><li>第4天：确定最低ICS的幅度，建立地方优先使用的非正式性位置偏爱调理协议。滴定脉冲1和2的振幅。典型的振幅值是20-80μA。 </li><li>从第5天：提供ICS的奖励来训练大鼠就绪地区与东部和西部影像展示与我联系起来CS奖励。继续下去，直到老鼠是东方和西方的图像区域之间交替。 </li></ol></li><li>中间成形（ 图2B）。 <ol><li>引入白噪声（50 dB）到信号审判的开始。关闭白噪声时，大鼠进入准备区。 </li><li>自动化ICS交付进入已准备好面积，并成功完成“准备位置”。调整ICS交割的条目，并成功“准备位置”，加强行为的可能性。 注：手动调节的奖励概率塑造过程中，以配合个别老鼠的表现。减少奖励的概率为进入已准备好面积和维持成功的准备位置。奖励为完成成功“准备持仓建议末期概率为5-10％。大鼠奖励都是正确的选择。 </li><li>开始短“准备位置”的持续时间（ 例如 200毫秒）。逐步提高“准备位置”硬膜系统蒸发散在100毫秒步骤。 </li><li>打开白噪声如果老鼠过早打破了“准备位置”，使大鼠具有重新启动审判。 </li><li>移动到后期整形时，老鼠被捧在“准备位置”长达1200毫秒。 </li></ol></li><li>末成形（ 图2C）。 注：在后期整形训练是特定于该鼠将执行的任务。在所有的任务参数的精确和公正的控制这一步成型自动化培训，但保持灵活性，以手动提供ICS奖励。为两个任务的训练方案进行了描述。 <ol><li>视觉双条件的歧视（vBCD）任务：使用不同的视觉刺激训练大鼠一个简单的形状和亮度discriminence。 <ol><li>通过打开白噪声开始试用。 </li><li>随机处以700“准备位置”延迟 - 1,200毫秒。 </li><li>手动提供ICS如果需要，加强成功的&#39;准备好婆sitions“。 </li><li>呈现一对图像中的图像显示区域。伪随机提供正确的图像上的图像区域的左侧或右侧。 </li><li> ICS提供一个正确的响应和清除地板上。当老鼠进入其中正确的图像所在的区域正确的响应被注册。在培训的第一天只，发行75分贝一阵白噪声作为一种威慑的一个不正确的响应。 </li><li>发出了不正确的审判后的校正试验。校正试验具有相同的参数（左侧或右侧和“准备位置”延迟）如前面不正确的审判。 </li><li>一旦老鼠能够成功地执行简单的歧视 ，引入不同楼层的模式来训练双条件判别规则。 </li><li>提出了一种新的图像对和两个不同的地板图案作为上下文。正确的图像是待地板图案; 如黑站r是正确的，当楼是灰色和白色圆圈是正确的，当地板条纹（ 图3C）。 </li><li>伪随机地分配在地板图案和对于每个试验确保试验是平衡的正确图像的位置（左或右）。 </li><li>一个不正确的试验中，试验参数与前面的审判后执行校正试验。 </li></ol></li><li>视觉空间注意（VSA）任务：目前照明的白色圆圈在舞台上定义的空间位置来训练大鼠接近目标圆的空间位置。 注：对于这个任务竞技场有灰色圆圈在东部和西部地区的图像不同空间位置。经过成功的“准备位置”，目标圈将点亮（变白），以及鼠必须向那个目标位置（ 图3B）。 <ol><li>随机并处1,000-1,60“准备位置”延迟0毫秒的审判试点。 </li><li>手动提供ICS如果需要，加强成功的“准备位置”。 </li><li>的“准备位置”完成后，随机照亮灰色圆圈之一。 </li><li>交付的ICS时，大鼠进入照明圈的区域。 </li><li>关闭照明，并开始在对面（东或西）侧的下一个试验。 </li><li>在后期整形的开始，照亮了一圈，直到老鼠接近它，或者直到试用期结束（5秒照亮了一圈后）。每次试验得分为正确或遗漏审判。对于遗漏的试验，照亮了整层（白层提交），并没有回报将持续到下一个试验。 </li><li>当老鼠的性能达到80％的正确，减少了时间的循环会一直发出1秒的金额。大鼠有5秒做出选择。 </li><li>不奖励不正确的试验。开始下一次试验。 </li><li>如果有遗漏的三人，照亮地板，并开始一个新的审判。 </li><li>在80％的正确进一步减少目标圈亮起，以500毫秒的时间。 </li><li>随机每次试验前选择目标位置。大鼠将继续有5秒做出选择之前，整个地板照亮的信号，试验结束。 </li><li>不奖励的不正确或遗漏试验。大鼠必须启动在舞台的另一侧进行新的审判。 </li><li> 注：其他各界可以在每个图像区域被添加到进一步增加任务的难度。 </li></ol></li></ol></li></ol>

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我们正式描述协议来训练老鼠在地板投影迷宫完全自动化的复杂的视觉认知任务。地板投影迷宫已经被成功地用于在上一个2选视觉辨别任务1的性能建立对象定位连词和误差信号的神经关联的postrhinal皮质。 行为整形协议被设计为灵活的，以便它可以被调整以适应个体大鼠的学习速率。对于行为系统编写定制代码允许实验者在训练控制的自动化ICS交货的关键步骤的可能性; 如训练“准备位置”。该代码也应该允许人工送ICS的过程中使用一个可编程的按钮盒。早期整形的目的是要建立有效的ICS的刺激奖励交货加强行为。如果可能的话，我们建议植入STImulating电极双侧入MFB的情况下，无效的刺激在一个半球。我们的经验，但是，一直几乎所有植入电极的ICS已经功能，提供一个有益的刺激。中级成型阶段是训练大鼠维持在准备好面积一个“准备位置”的关键。在“准备位置”，老鼠应该是静止的它的鼻子指向这里选择的图像将被呈现的图像区域。在“准备位置”控制时，显示图像，从这些大鼠接近的图像和从该鼠观看的图像的距离的方向。我们建议安装在老鼠的探头来监控在老鼠的头部指向为更好地控制行为和目标图像呈现更精确地控制方向跟踪的LED。能发出手动传送ICS的培养大鼠保持适当的“准备位置＆＃8217;当老鼠被保持在每个审判满意“准备位置”，在培训后期整形是任务明确。在后期整形老鼠被训练来学习特定的规则来完成既定任务。 我们使用ICS作为我们的奖励交付的方法，因为此方法提供即时反馈，以导致更快的学习过程中的行为塑造的大鼠，并收集在自动化任务的神经数据时更完成的试验在一个会话。 ICS交货，但是，导致电的工件在神经的录音，并且可以是有问题的，用于分析连续LFP或多组数据。周围的电气神器的间隔可以从下线之前连续数据分析神经记录数据文件中删除。从高通滤波尖峰数据ICS定型的工件可以离线很容易地删除，而不会影响单穗分析。对于地板投影迷宫协议的​​未来优化包括使用optogenETIC工具来提供内部奖励，以减少和消除与电刺激相关的文物。 地板投影迷宫优化了大鼠视觉功能，因而更适合视觉引导行为的任务。应当指出的是直接比较不能实验范式在地板投影迷宫和操作室之间，因为成功收购一个给定的任务采用不同的实验方案和标准不同的定义作出。我们先前的研究显示，但是，老鼠获得一个简单的2选视觉辨别任务〜50次试验在地面投影迷宫2与&gt; 300试验在影像操作性商会3,10垂直已提交其他研究相比。 VSA的任务（5-CSRT）旨在评估视觉注意力经典的5 -选择串行反应任务13为蓝本流程。通常是5-CSRT是在一个操作性室，并要求该动物，使鼻子戳在由光闪光指示的适当鼻戳孔;这里VSA的任务是在一个开放，其中动物必须保持固定在舞台上的特定位置，引导他们关注的目标位置，并等待出现的光刺激。根据我们的经验，鼠须〜3,200试验，以在5-CSRT用14〜800试验的VSA任务在地板投影迷宫相比，达到标准（75％连续两天）。 在地板上投影迷宫进行行为任务的另一个好处是，任务是在一个大型的开放式舞台，它利用大鼠的自然倾向去探索它的环境，而不是需要动物来修复其目光投向一个任务开展静止目标。利用自由活动大鼠在一个开放的舞台和的一个主要优点＃160;在地上投影迷宫装置是，这两个非自我中心和自我中心的空间信息可以被收集以视觉信息。本范例的另一个优点是，任务不必限于介绍的静态图像。位置和视觉刺激是动态的功能可以在今后的任务中使用。使用影城行为研究系统的跟踪能力，任务可以为一个给定的大脑结构的更详细的功能的了解来开发的。同时结合电生理记录与视觉引导的认知任务，为大脑活动是如何与认知过程，如决策和视觉识别的基本问题可以探讨。 使用视觉引导的任务，从大鼠的研究发现可以得到更好的翻译对人类与提供的疗法为人类认知疾病的最终目的。

视觉任务通常用于人类和猴子的研究中，研究机制，基本的学习和记忆。啮齿动物模型中，但是，更易于接触到的研究人员对于较大规模，更好控制的研究，并有允许更多的侵袭性电生理技术的附加优点。与其它方法，如遗传操作，电生理记录在自由活动大鼠的组合提供了精确的瞄准机制和电路的基本认知过程的有用模型。灵长类动物的视觉任务要求被试直接凝视视觉刺激在监视器上，而大鼠任务要求被试与环境互动。地板投影迷宫利用大鼠，积极探索环境，同时抓视觉刺激的自然倾向。 使用专为啮齿动物设计的触摸屏设备的认知任务已允许更好的翻译结果由啮齿类动物模型到人类3。触摸屏任务都典型地在一个腔室与垂直呈现在墙上3-7二维视觉刺激。这些触摸屏任务要​​求受试者为达致该目标视觉刺激后，打破了红外线光子束或按上一压垫来注册其响应。解剖学和行为的证据，但是，建议，老鼠在较低的视觉半侧更有效地处理视觉信息指导行为8-10。我们实验室已经开发利用地投影迷宫2认知任务中的二维视觉刺激都回投射到测试舞台的地板上。在地板投影迷宫老鼠可以在大型的开放式舞台在执行任务时与触摸屏设备相比进行跟踪。因此，可以在除了视觉信息的神经相关因素来获得在记录神经活动的空间信息ð决策。 我们向内侧前脑束（MFB）交付颅内刺激（ICS）作为奖励11。奖励交付该方法具有对食品和饮料的回报优势。食品和饮料的奖励可导致饱食，甚至在食物被剥夺大鼠，限制试验次数的动物将执行，并可能减缓训练过程。 ICS提供即时奖励提供对任务绩效的即时反馈。即时奖励成果更快整形和收购，大幅降低培训协议的期限。此外，试验中的较大数目可以在一个会话内完成，提高了数据的收集量，并导致任务相关的行为的一个更可靠的样品。 使用地板投影迷宫，我们将描述一个通用协议，以塑造大鼠的行为，以执行复杂的认知任务。氏的一般协议提供了跨多种目前用于记录的注意力和视觉识别1神经相关的任务训练大鼠的框架。因此，地板投影迷宫优化了视觉大鼠的能力，并允许比较强，在人类和非人类灵长类动物的视觉任务。

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automated visual cognitive tasks for recording neural activity using a floor projection maze

在灵长类动物用于研究学习和记忆的神经生理机制的任务通常是视觉引导的认知任务。我们已经开发了视觉认知任务使用的地板投影迷宫1,2，这对于大鼠允许更强的实验结果与其他物种的对比视觉能力的优化作用。 为了探讨学习和记忆的神经关联，我们已经整合电生理记录到在地板上投影迷宫1,2全自动的认知任务。接口与动物跟踪系统行为的软件可以监控与图像呈现的精确控制动物的行为和奖励意外事件更好的受过训练的动物。用体内电生理记录系统集成，使检查神经活动的行为相关因素在给定的认知任务选择的时代。&lt;/ P&gt; 我们描述相结合，以啮齿动物和颅内奖励与电生理方法自动化视觉呈现的信息模​​型系统的协议。我们的模型系统提供了先进的工具集作为一个框架，其他认知任务，以更好地隔离和识别造成特定的认知过程的具体机制。

一般整形步骤，我们的目标是适应大鼠的试验舞台，培养大鼠保持在一个固定的“准备位置”为目标视觉刺激的呈现，并接近正确的视觉刺激的位置。习惯到检测室，舞台，系绳后，早期整形通常需要100-150试验，直至大鼠竞技场的东，西两侧交替。在早期塑造大鼠通常是通过已准备好面积在竞技场的中心运行，并花费大部分的时间探索舞台（ 图4A）的周长。老鼠在中间成形阶段逐步学会以维持已准备好面积固定的“准备位置”，要求600-700试验。在这一点上，动物的路径都是千篇一律从已准备好面积环的图像区域用更少的时间花在探索迷宫的周长。然而，鼠不保持一个固定的“准备好婆sition&#39;，由在哪个大鼠遍历中心准备好面积（ 图4B）的速度来表示。 由中级整形月底，大鼠接近目标视觉刺激之前保持在准备好面积固定的“准备位置”。大鼠然后启动对舞台（ 图4C）的另一侧的下一个试验。 跟踪软件及神经数据采集系统与行为控制系统的集成使得神经数据的事件相关分析。可驱动的电极阵列可策略性地放置记录单单元和局部场电位活动。录音，进行了postrhinal皮质当老鼠进行的vBCD任务。 Perievent直方图和光栅图显示，细胞在postrhinal皮质到目标视觉刺激的发生和在地板图案（ 图5A）的发生作出响应。在为r的后顶叶皮层的ats执行VSA任务的细胞响应的图像显示，并且当选择是由进入该定义的对象图像（ 图5B）的区域。在VSA中的任务表现在后顶叶皮层局部场电位活动显示出强大的力量在西塔范围（〜8赫兹）时，老鼠是在图像呈现（ 图5C）前的“准备位置”。 <img alt="图1" fo:content-width="5in" fo:src="/files/ftp_upload/51316/51316fig1highres.jpg" src="/files/ftp_upload/51316/51316fig1.jpg" width="400" /> 图1实验装置。的行为和控制室A原理图。地板投影迷宫坐落在行为空间。大鼠通过一个顶置式照相机监视。中控室设有设备控制任务，并收集神经的数据。的B.尺寸该领结迷宫。C.抓屏影城工作室。区是由用户定义的。合乎逻辑的事件将作为影城的数字输出来对行为控制系统集团（Med联营公司）监测大鼠的进度。 <a href="https://www.jove.com/files/ftp_upload/51316/51316fig1highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图2" fo:content-width="5in" fo:src="/files/ftp_upload/51316/51316fig2highres.jpg" src="/files/ftp_upload/51316/51316fig2.jpg" /> 图2。的整形步骤：A.在早期塑造大鼠示意图收到ICS用于输入已准备好面积，并在进入东，西图像区域。其目的是培养大鼠这些地区与ICS的奖励。B.中级整形重在培养的大鼠维持在准备好面积固定的“准备位置”相关联。这些图像呈现ONL维持一个成功的“准备位置”后，年。大鼠继续获得ICS的逼近图像中的图像区域。C.在后期整形，大鼠成功保持一个固定的“准备位置”。训练是特定的任务，老鼠被训练来学习特定的规则来完成既定任务。闪电表示ICS交货。 <a href="https://www.jove.com/files/ftp_upload/51316/51316fig2highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图3" fo:content-width="5in" fo:src="/files/ftp_upload/51316/51316fig3highres.jpg" src="/files/ftp_upload/51316/51316fig3.jpg" /> 图3。A.原理图vBCD任务当楼是灰色的，黑色的明星是奖励;。当地板条纹，白色圆圈是奖励乙 。原理非常重大收购任务。灰色圆圈表示在图像领域的目标位置。目标激励是其中一个圆形的简单（500毫秒）照明（白色）。在大鼠奖励接近正确的目标位置。 <a href="https://www.jove.com/files/ftp_upload/51316/51316fig3highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图4" fo:content-width="5in" fo:src="/files/ftp_upload/51316/51316fig4highres.jpg" src="/files/ftp_upload/51316/51316fig4.jpg" /> 图4。从执行在不同的整形步骤鼠两分钟的片段整形。位置数据中示例路径 。动物的速度是由热图表示。冷色调代表最慢的速度和热的颜色代表最快速度。 答：在早期塑造大鼠探索和后部了东方和西方的图像区域的外墙上，也不属于已准备好面积：B在停止。一个千篇一律的路径开始在中级SH涌现APING。路径形成对图像区域循环回已准备好面积。大鼠开始成功地维持已准备好面积。℃的 “准备位置”。当大鼠升入后期整形，大鼠保持静止“准备位置”和大鼠的路径是更刻板。 <a href="https://www.jove.com/files/ftp_upload/51316/51316fig4highres.jpg" target="_blank">点击这里查看大图。</a> <img alt="图5" fo:content-width="5in" fo:src="/files/ftp_upload/51316/51316fig5highres.jpg" src="/files/ftp_upload/51316/51316fig5.jpg" /> 图5。的perievent相关分析实例A。该vBCD任务与不同的反应到目标图像（左）的介绍，和地板（右）。B的演示过程中从postrhinal皮层记录细胞。在从后顶叶皮层细胞记录VSA的任务有不同的反应，以圆（左）的照明。选择的空间位置在目标圆照（右）。℃后增加射击。谱图显示出强劲的动力西塔在后顶叶皮层在“准备位置”。垂直红线表示成功的“准备位置”和图像的演示文稿的末尾。垂直蓝线表示1楼在审判演示开始在vBCD任务。垂直绿线表示一个选择是注册在VSA的任务。 <a href="https://www.jove.com/files/ftp_upload/51316/51316fig5highres.jpg" target="_blank">点击这里查看大图。</a>

Watch this Scientific Journal Video about Automated Visual Cognitive Tasks for Recording Neural Activity Using a Floor Projection Maze at JoVE.com

Automated Visual Cognitive Tasks for Recording Neural Activity Using a Floor Projection Maze

我们描述了地板上投影迷宫训练大鼠慢性电生理记录在完全自动化的认知任务的协议。

使用地面投影迷宫自动化视觉认知任务记录神经活动

Neuropsychological tasks used in primates to investigate mechanisms of learning and memory are typically visually guided cognitive tasks. We have ...

automated-visual-cognitive-tasks-for-recording-neural-activity-using

Research

JoVE Journal

Behavior

13.0K 次观看.  Brown University. 我们描述了地板上投影迷宫训练大鼠慢性电生理记录在完全自动化的认知任务的协议。 

视频: Automated Visual Cognitive Tasks for Recording Neural Activity Using a Floor Projection Maze

Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the &#34;cloud&#34; and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in&#160;cabinet; two such cabinets (16 environments) may be controlled by one computer.

Fully automated system for measuring physiologically meaningful properties of the mechanisms mediating spatial localization, temporal localization, duration, rate&#160;and probability estimation, risk assessment, impulsivity, and the accuracy and precision of memory, in order to assess the effects of genetic and pharmacological manipulations on foundational mechanisms of cognition in mice.

小鼠自动化，定量认知/行为筛选：对于遗传学，药理学，动物认知与本科教学

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and ...

科研

行为学

A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. Higher cognitive functions that require precise control over sensorimotor responses such as decision-making and attentional modulation, however, are typically assessed in nonhuman primates. Despite the richness of primate behavior that allows multiple variants of these functions to be studied, the rodent model remains an attractive, cost-effective alternative to primate models. Furthermore, the ability to fully automate operant conditioning in rodents adds unique advantages over the labor intensive training of nonhuman primates while studying a broad range of these complex functions.
Here, we introduce a protocol for operantly conditioning rats on performing working memory tasks. During critical epochs of the task, the protocol ensures that the animal's overt movement is minimized by requiring the animal to 'fixate' until a Go cue is delivered, akin to nonhuman primate experimental design. A simple two alternative forced choice task is implemented to demonstrate the performance. We discuss the application of this paradigm to other tasks.

A fully automated protocol for rodent operant conditioning is proposed. The protocol relies on precise temporal control of behavioral events to investigate the extent to which this control influences neural activity underlying sensorimotor integration and cognitive control experiments.

为感觉运动整合与认知控制实验完全自动化的啮齿动物调理协议

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. ...

Uncovering Beat Deafness: Detecting Rhythm Disorders with Synchronized Finger Tapping and Perceptual Timing Tasks

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson&#8217;s disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

Behavioral tasks that allow for the assessment of perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) are presented. Synchronization of finger tapping to the beat of an auditory stimuli and detecting rhythmic irregularities provides a means of uncovering rhythm disorders.

揭开节拍耳聋：检测节律紊乱与同步手指敲击和感知定时任务

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here ...

Practical Methodology of Cognitive Tasks Within a Navigational Assessment

This paper describes an approach for measuring navigation accuracy relative to cognitive skills. The methodology behind the assessment will thus be clearly outlined in a step-by-step manner. Navigational skills are important when trying to find symbols within a speech-generating device (SGD) that has a dynamic screen and taxonomical organization. The following skills have been found to impact children&#8217;s ability to find symbols when navigating within the levels of an SGD: sustained attention, categorization, cognitive flexibility, and fluid reasoning1,2. According to past studies, working memory was not correlated with navigation1,2.
The materials needed for this method include a computerized tablet, an augmentative and alternative communication application, a booklet of symbols, and the Leiter International Performance Scale-Revised (Leiter-R)3. This method has been used in two previous studies. Robillard, Mayer-Crittenden, Roy-Charland, Minor-Corriveau and B&#233;langer1 assessed typically developing children, while Rondeau, Robillard and Roy-Charland2 assessed children and adolescents with a diagnosis of Autism Spectrum Disorder. The direct observation of this method will facilitate the replication of this study for researchers. It will also help clinicians that work with children who have complex communication needs to determine the children&#8217;s ability to navigate an SGD with taxonomical categorization.

Children who have complex communication needs can benefit from the use of a speech-generating device (SGD). Cognitive skills were identified as having an impact on the ability to navigate between levels of SGDs. This protocol describes the steps needed for Speech-language Pathologists to assess cognitive skills and navigational abilities.

认知任务的实用方法在一个导航评估

This paper describes an approach for measuring navigation accuracy relative to cognitive skills. The methodology behind the assessment will thus be ...

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive &#8211; running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals&#8217; wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Here we present a protocol to induce activity-based anorexia (ABA) in female adolescent mice. ABA is a condition of hyperactivity evoked by imposing food restriction on rodents with access to a running wheel. This phenomenon is being used as a model to study the underlying neurobiology of anorexia nervosa.

使用基于活动的厌食症啮齿动物模型来研究神经性厌食症的神经生物学基础

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A ...

Using Fiberless, Wearable fNIRS to Monitor Brain Activity in Real-world Cognitive Tasks

Functional Near Infrared Spectroscopy (fNIRS) is a neuroimaging technique that uses near-infrared light to monitor brain activity. Based on neurovascular coupling, fNIRS is able to measure the haemoglobin concentration changes secondary to neuronal activity. Compared to other neuroimaging techniques, fNIRS represents a good compromise in terms of spatial and temporal resolution. Moreover, it is portable, lightweight, less sensitive to motion artifacts and does not impose significant physical restraints. It is therefore appropriate to monitor a wide range of cognitive tasks (e.g., auditory, gait analysis, social interaction) and different age populations (e.g., new-borns, adults, elderly people). The recent development of fiberless fNIRS devices has opened the way to new applications in neuroscience research. This represents a unique opportunity to study functional activity during real-world tests, which can be more sensitive and accurate in assessing cognitive function and dysfunction than lab-based tests. This study explored the use of fiberless fNIRS to monitor brain activity during a real-world prospective memory task. This protocol is performed outside the lab and brain haemoglobin concentration changes are continuously measured over the prefrontal cortex while the subject walks around in order to accomplish several different tasks.

Monitoring brain activity outside the lab without physical constraints presents methodological challenges. A fiberless, wearable functional Near Infrared Spectroscopy (fNIRS) system was used to measure brain activity during an ecological prospective memory task. It was demonstrated that this system could be used to monitor brain activity during non-lab based experiments.

用无纤维，耐磨fNIRS监视在真实世界的认知任务脑活动

Functional Near Infrared Spectroscopy (fNIRS) is a neuroimaging technique that uses near-infrared light to monitor brain activity. Based on neurovascular ...

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 ...

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 ...

Integrating Visual Psychophysical Assays within a Y-Maze to Isolate the Role that Visual Features Play in Navigational Decisions

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired investigations into collective motion, specifically, their ability to integrate environmental and social information across ecological contexts. This demonstration illustrates techniques used for quantifying behavioral responses of fish, in this case, Golden Shiner (Notemigonus crysoleucas), to visual stimuli using computer visualization and digital image analysis. Recent advancements in computer visualization allow for empirical testing in the lab where visual features can be controlled and finely manipulated to isolate the mechanisms of social interactions. The purpose of this method is to isolate visual features that can influence the directional decisions of the individual, whether solitary or with groups. This protocol provides specifics on the physical Y-maze domain, recording equipment, settings and calibrations of the projector and animation, experimental steps and data analyses. These techniques demonstrate that computer animation can elicit biologically-meaningful responses. Moreover, the techniques are easily adaptable to test alternative hypotheses, domains, and species for a broad range of experimental applications. The use of virtual stimuli allows for the reduction and replacement of the number of live animals required, and consequently reduces laboratory overhead.
This demonstration tests the hypothesis that small relative differences in the movement speeds (2 body lengths per second) of virtual conspecifics will improve the speed and accuracy with which shiners follow the directional cues provided by the virtual silhouettes. Results show that shiners directional decisions are significantly affected by increases in the speed of the visual cues, even in the presence of background noise (67% image coherency). In the absence of any motion cues, subjects chose their directions at random. The relationship between decision speed and cue speed was variable and increases in cue speed had a modestly disproportionate influence on directional accuracy.

Here, we present a protocol to demonstrate a behavioral assay that quantifies how alternative visual features, such as motion cues, influence directional decisions in fish. Representative data are presented on the speed and accuracy where Golden Shiner (Notemigonus crysoleucas) follow virtual fish movements.

在 Y-Maze 中集成视觉心理物理分析,以隔离视觉特征在导航决策中扮演的角色

Collective animal behavior arises from individual motivations and social interactions that are critical for individual fitness. Fish have long inspired ...

Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats

The optomotor response and the Y-maze are behavioral tests useful for assessing visual and cognitive function, respectively. The optomotor response is a valuable tool to track changes in spatial frequency (SF) and contrast sensitivity (CS) thresholds over time in a number of retinal disease models, including diabetic retinopathy. Similarly, the Y-maze can be used to monitor spatial cognition (as measured by spontaneous alternation) and exploratory behavior (as measured by a number of entries) in a number of disease models that affect the central nervous system. Advantages of the optomotor response and the Y-maze include sensitivity, speed of testing, the use of innate responses (training is not needed), and the ability to be performed on awake (non-anesthetized) animals. Here, protocols are described for both the optomotor response and the Y-maze and examples of their use shown in models of Type I and Type II diabetes. Methods include preparation of rodents and equipment, performance of the optomotor response and the Y-maze, and post-test data analysis.

Neural degeneration in both eyes and brain as a result of diabetes can be observed through behavioral tests carried out on rodents. The Y-maze, a measure of spatial cognition, and the optomotor response, a measure of visual function, both provide insight into potential diagnoses and treatments.

通过视运动反应进行视觉功能的行为评估，通过Y迷宫对糖尿病大鼠的认知功能进行行为评估

The optomotor response and the Y-maze are behavioral tests useful for assessing visual and cognitive function, respectively. The optomotor response is a ...