我们感谢教师研究理事会梓太平洋大学的资金支持。我们也感谢施耐德阿什利，迈克尔·格雷格和汉娜样的技术支持。

这项研究是经梓太平洋大学机构动物护理和使用委员会。所有涉及动物的程序进行了以下的指南实验动物的护理和使用来自美国国立卫生研究院的建议。 1.修改设备的社会动机和价对比测试范式<ol><li>为了测试小鼠的社会行为的操作性任务，修改中心通道模块化梭箱。这些穿梭箱测量44厘米×17.3厘米和由有机玻璃和不锈钢。 </li><li>通过安装一个线栅的门框的面修改可编程闸门。线栅应允许有限的社会接触，但不使小鼠跨越从一个腔室到另一个。 </li><li>使用可编程闸门，将每个箱子分成两个腔:每个测量约22厘米×17.3厘米。指定一个腔室中日Ë试验箱和其他作为靶室。 </li><li>将鼠标杠杆在相反的断头台门墙的试验室。将两个鼠标杆之间的液体食物瓢插座。 </li><li>程序鼠标杆要么打开闸门或呈现液体食物奖励，这取决于测试的范例。 </li><li>连接手持按钮的装置和程序，开启闸门（用于测试小鼠的手动整形）。 </li><li>适合每个穿梭箱与一个八信道的I / R控制器横跨各室的金属网格地板监视活动。装入USB数字视频摄像机的测试室的上方，并将其连接到一台计算机。括三聚氰胺声音衰减隔间内的整个装置。 </li><li>运行使用写在实验室定制方案操作性程序。 </li></ol> 2.塑造小鼠，为社会动机范式<ol><li>将测试鼠标在试验Chamber及年龄，性别相匹配的刺激小鼠的靶室。 </li><li>训练测试鼠标按下杠杆打开使用成型或连续逼近加固到所需操作反应的方法中的闸门。在此成形过程中，通过按下编程以控制闸门手持按钮手动递送加固。 注意:加固由穿过线栅打开闸门15秒，从而允许访问刺激小鼠。 </li><li>观察鼠标在使用相机安装在试验室上方的测试室。 </li><li>训练每只小鼠在一系列30分钟的日常会话，直到他们证明至少有10操作性响应（杠杆压力机）中有3个连续5届的测试。通过使用随机分配班车盒旋转老鼠。 </li><li>如果小鼠后30天的培训课程没有达到这个标准，请从实验和DESI小鼠gnate非学习者。 注:每日培训课程的数量可以延长到30取决于研究者的偏好。 </li><li>交替成形，使得不同的小鼠用于每隔一天期间使用的刺激小鼠。 </li><li>用70％乙醇每次训练之间穿梭清洁箱。此外，在完成用消毒清洁剂，每天测试，所有设备的下面。 </li></ol> 3.测试中的社会动范式小鼠<ol><li>放置在试验室训练有素的试验小鼠和年龄和性别匹配的刺激小鼠在靶室。在测试过程中，使用至少10个刺激小鼠池分配给每个测试鼠标，使刺激小鼠后，10每天测试会议只是重复。不使用成形用于在测试期间所使用的刺激小鼠。 </li><li>程序闸门打开钢筋上的进步比进度，使得操作性重数量必要获得的15秒访问目标鼠标的社会报酬sponses（杠杆压力机）算术由3每次试验的固定速率增加。 </li><li>程序测试会话结束时，测试鼠标停止杆挤压连续五分钟。 </li><li>记录的最后完成的（增强）之比为断点。使用此相关的措施，因为社会动机的一个指标。测试每只小鼠连续20届每天或至少10测试阶段后，渐近性能水平观察。 </li><li>擦拭用70％的乙醇和完成使用消毒洗涤剂每天测试的以下各个测试会话之间穿梭盒子。 </li></ol>社会的4价比较对战食物奖赏<ol><li>毕竟小鼠完成的社会动模式，旨在向社会悬赏的价与食物奖励的对比任务测试这些小鼠相同。 </li><li>计划一个杠杆打开闸门和呈现社会报酬为15秒和编程相反杆呈现的液体食物奖励15秒。 注:在本协议中所用的液体食物奖励包括淡奶甜与0.2％的蔗糖。反复呈现的0.02毫升奖励给每个小鼠制备足够量（通常是500ml）中。 </li><li>指定测试小鼠交替杆/回报突发来控制小鼠之间潜在的杠杆偏见。因此，分配一半的小鼠每个测试组中，以左杆/食物奖励，右杆/社会应急奖励，另一半为左杆/社会回报和右杆/食物奖励应急。 </li><li>培养小鼠与社会食物奖励的价比较。 <ol><li>将测试鼠标在试验室，并把年龄和性别匹配的刺激鼠标在靶室。 </li><li>只作一个杠杆/每次训练期间应急奖励活跃。培训包括每天偶然性之间轮流6 1小时的会议。分配给每个鼠标测试每其他社会奖励备选会议小鼠的刺激。 </li><li>在训练和测试用食物奖励维持其自由采食食物饮食小鼠。食物剥夺是不必要的小鼠与使用淡炼乳和蔗糖溶液18的操作条件。 </li></ol></li><li>测试小鼠与社会食物奖励的价比较。 <ol><li>编程钢筋的时间表以3固定比率:1，使每一个第三杆压被加强，而仅由它的各个相关联的奖励。 </li><li>程序测试会运行60分钟。 </li><li>将测试鼠标在试验室，并把年龄和性别匹配的刺激鼠标在靶室。注:在社会动机任务中使用10刺激小鼠相同的池可以再次使用，但分配到使用10天循环测试小鼠。 </li><li>特ST小鼠在以下6天的培训，或为后续观察渐近性能水平至少每天10届20届日报。对于这个范例的主要依赖措施是杠杆压力机每个奖励类型的总数。 </li><li>再次，擦拭用70％乙醇和下面的每个测试日使用消毒清洁剂测试会话之间穿梭箱。 </li></ol></li></ol>

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作者有没有竞争的财务权益。

在这篇文章中所描述的操作性的社会范式的动机是在人类疾病的小鼠模型社会行为的表征功能强大的工具。而不是让一个测试鼠标选择被动地社会的遭遇，这些范式需要从测试鼠标的努力，才能获得社会的回报。的努力，测试鼠标愿意生产，以获得社会报酬的数额提供的社会动机的定量测量。此外，通过比较价模式，激励行为可以在不同类型的奖励相比。这两个操作性范例可以用于通过呈现适当的刺激的闸刀门的另一侧，以评估性和亲动机为好。 这些社会动机范式的发展涉及到的几个关键变量的处理方法。例如，通过试点研究的时间量，社会奖励我š呈现降低从30秒到15秒。而这一次是足够的试验和刺激的小鼠之间的社会交往，今后的研究可以优化的时间量为社会奖励。同样，杠杆压力机社会回报的递增比例从5到3基于研究试点固定利率降低。 必要的天数达到渐近杆挤压行为，通过日常测试会议后的30天内进行初步评估。经测定，大部分小鼠达到渐近线7天，以便测试会话数降至20日的表现也不过波动，所以在最后10天的平均数据，确保渐近性能，同时还提供了真正的平均性能更好的指标不是更少的测试天。研究人员应监控其数据，以确保在10天的测试达到渐近性能或协议为根据需要修改。 TRA进不去会议还下调1小时至30分钟。不依赖于鼠标应变所需的培训和一些老鼠的数量可以任意指定为培训班18固定数量后nonlearners。对要达到的标准晋升的测试模式培训天数提供的社会动机的另一个指标，因此是值得跟踪。研究人员还可能要进行实验的比较价不同范式食物奖励的选项。但是，重要的是，在测试的小鼠最初训练有素使用纯粹社会报酬，然后开始价比较范例之前在社会动机范例测试。 这些操作性社会动机范例可以修改和通过测量高于上述协议表示的附加变量提高时。例如，每只小鼠在其各自的腔室的位置可以使用Cu被跟踪rrently提供商业软件。此外，可以在社会交往打进特定的行为，包括鼻对鼻的接触或超声波发声。研究人员可以进一步的实验与调整中的社会动范式或涉及缺乏社会合作伙伴，甚至涉及到后面的闸门等刺激比较试验中使用的比例，如一个同种甚至是傀儡的视频。对于比较价范式，分析动态选择跨试验可以提供关于因饱食为特定类型的奖励轮班18动机的进一步信息。 虽然这些操作性的社会动机范式提供了急需的工具，在小鼠量化社会的动机，他们确实有一定的局限性。首先，这些范式要​​求老鼠有认知能力，使杆挤压和社会收益之间的关联了解到。某些小鼠模型可能在认知和社交能力的缺陷使之难以利用这些范式评估社会动机。第二，社会遭遇的性质是有限的小鼠只允许跨越的线栅相互作用。然而，老鼠仍然能够成功地参与许多典型的社会行为，最值得注意的是，鼻对鼻的调查。这些方法之一最终限制是，它们是劳动密集型的，并且需要大量的时间来完成的。通过两种范例的训练和测试需要至少每日会话两个月。有些小鼠可能需要更长的时间来学习杆压关联拉伸会话所需数量。而范式当然没有资格作为高通量技术，它们生成的数据是非常有价值的，值得所需的劳动力投入。然而，为了提供特定的小鼠模型的社会行为的更充分的表征，所以建议这些范式是我们编与测量小鼠社会行为的建立等方法结合。

近年来，遗传和环境因素的社会行为，包括自闭症谱系障碍，病症的联系，导致了设计的探索这些因素在社会行为中的作用的小鼠模型的发展。这创造了在小鼠的社会行为的特征的新技术，包括社会动机1的定量测量的要求。 有几个建立范例，可以用来然而展示社会动机在小鼠;他们都有自己的量化行为动机的强弱能力的严重限制。例如，一些早期行为评估包括那些从来没有见过两只小老鼠之间的社会互动的简单的观察。几个行为包括将至，下面，嗅和疏导经常测量，并且可以提供社会积极性的一个指标。这些研究最初进行大鼠2-5，再后来改编为小鼠6,7使用。习惯化/ dishabituation社会识别范例，其中试验动物反复暴露于相同的刺激动物（习惯化），然后暴露于一种新型动物（dishabituation）也提供社会动机8的测量结果。作为标签表明，典型的动物会显示给相同的刺激动物的重复存在一个习惯于行为反应，但将演示dishabituation，或返回到基线时，当暴露于新的动物。在习惯反应可能表明在测试鼠标的积极性的下降与刺激小鼠互动。社会选择范例允许测试鼠标到空室和刺激小鼠限制在不同室之间选择也被用来评估社会动机。试用通常首先将测试鼠标在一个中立的，中心室。这个任务的某些版本涉及牛逼ethering刺激老鼠一腔9。此任务的一种修改中采用的使用金属丝外壳上的刺激小鼠避免刺激动物10的束缚。最近，社会条件性位置偏爱任务被开发，其中小鼠被调节以视觉上不同的腔室与任一的存在或不存在一个社会伙伴的，然后使其探索空腔室以下调理11相关联。更多的时间在室内度过的社会配对以前发生的位置被认为是社会动机的一个指标。 所有上述范例提供与小鼠的社会表型的重要数据。然而，尽管人们可以观察到鼠标是否显示了"欲望"，寻求在上述范式社会交往，这种"欲望"， 即 ，社会的动机，实力是很难衡量的。的行为动机的强度有传统上被测量啮齿动物通过创建一种方案，其中它们具有以获得他们的动机源工作。这通常涉及啮齿动物训练在操作性范式涉及食品作为激励因素。然而，该方法以前已经用于研究社会动机大鼠，但无论是涉及获得性伴侣为雄性大鼠或，对于女性，获得自己的幼仔12,13（在Matthews 等人，2005中综述）。 此前下面描述的社会动范式的发展，只有一个社会调查的动机性动机之外使用操作性的模式小鼠12等研究。在这一系列的实验中，远交瑞士韦伯斯特小鼠进行了培训，按一个杠杆，以获得一个同性同种。在一项实验中，一个显著减少延迟开始响应的访问目标鳞状ê表现在单独圈养小鼠相比，群养小鼠建议增加的动机，寻求在这些社会孤立的小鼠的社会服务。在同一研究中的另一个实验中，比较了盐水和催产素拮抗剂（阿托西班）注入小鼠之间进行比较。有趣的是，药物注入小鼠表现出显著增加延迟时间，以应对开始访问目标服务器鼠标提示主动性降低了社会报酬在这些小鼠。 虽然这些实验代表了贵金属试图量化社会动机小鼠使用操作性条件，他们也被高度限制和在使用时的下述方法有很大提高。例如，在第一个实验中一个明显的根本缺陷上述（实际研究的实验2​​）是研究人员仅使用2跨测试天交替目标老鼠。此前有研究表明，社会认可，在群养老鼠可以持续至少7天从而降低社会调查与反复暴露于相同的目标14。然而，社会认可在单独圈养大鼠和小鼠中1消散- 2小时，使得社会调查的持续时间保持在基准水平，如果一个重复暴露于相同的靶是初始曝光15-17后至少2小时。单独圈养小鼠的降低延迟开始响应的报道，在马修斯社会访问等人的实验可能是缺乏跨测试天12社会识别靶小鼠的结果。这种潜在的变乱是通过使用一种新的靶小鼠在每个试验日，在下面的方法来控制对。此外，在从Matthews 等。研究两个实验如上所述，没有报告在组之间进行杠杆压力机的总数不同。这可能是在总杠杆压力机的差可能是恩，如果检测的研究人员利用的反应逐渐增加的比例，以奖励在我们下面列出的研究设计中使用。此外，访问目标小鼠手动控制被实验者，通过抬起一个盒子，覆盖了目标。用于访问目标鼠标使用一种自动控闸刀门的消除伪影的可能性由于实验者的存在。事实上，为了完全自动化的社会动操作性范式，研究设备进行了定制，详情如下。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Modular Shuttle Box</td>
			<td>Med Associates Inc.</td>
			<td>ENV-010MC</td>
			<td></td>
		</tr>
		<tr>
			<td>Auto-Guillotine Door&#160;</td>
			<td>Med Associates Inc.</td>
			<td>ENV-010B</td>
			<td></td>
		</tr>
		<tr>
			<td>Mouse Levers&#160;</td>
			<td>Med Associates Inc.</td>
			<td>ENV-3010M</td>
			<td></td>
		</tr>
		<tr>
			<td>Liquid Dipper with Food Receptacle</td>
			<td>Med Associates Inc.</td>
			<td>ENV-202M-S</td>
			<td></td>
		</tr>
		<tr>
			<td>Eight-Channel I/R Controller&#160;</td>
			<td>Med Associates Inc.</td>
			<td>ENV-253C</td>
			<td></td>
		</tr>
		<tr>
			<td>Melamine Sound-Attenuating Cubicle&#160;</td>
			<td>Med Associates Inc.</td>
			<td>ENV-016MD</td>
			<td></td>
		</tr>
		<tr>
			<td>MED-PC IV Software Program</td>
			<td>Med Associates Inc.</td>
			<td>MED-PC IV&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Microsoft Lifecam Camera&#160;</td>
			<td>Microsoft</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Wire Grid</td>
			<td></td>
			<td></td>
			<td>Wire grids can be purchases from a hardward store. We cut wire grids from stainless steel mouse cage tops.&#160;</td>
		</tr>
		<tr>
			<td>70% Ethyl Alcohol</td>
			<td></td>
			<td></td>
			<td>Used to clean shuttle boxes between mice. Specific brand is unnecessary.</td>
		</tr>
		<tr>
			<td>Evaportated Milk</td>
			<td>Carnation</td>
			<td></td>
			<td>0.02 mL combined with 0.2% sucrose. We always purchase the same brand for better consistency.&#160;</td>
		</tr>
		<tr>
			<td>Sucrose</td>
			<td></td>
			<td></td>
			<td>Any brand of pure granular sugar will due as it is dissolved in the evaporated milk.&#160;</td>
		</tr>
	</tbody>
</table>

quantifying social motivation in mice using operant conditioning

在这个协议中，社会动机是通过一对操作条件反射范式测量小鼠。为了进行实验，两腔梭箱分别配备有两个操作性杆（左和右）和一个食品贮器在一个室中，然后从所述第二腔室由自动闸门覆盖的线栅分割。不同的刺激小鼠，在整个旋转测试天，出任线栅背后的社会刺激，以及闸门的开启以下是唯一可见的。试验鼠进行了培训，以杠杆压，以打开门，获得刺激合作伙伴，持续15秒。获得社会报酬所需杠杆压力机的数量逐步增加对3.测试会话固定时间表结束后测试小鼠停止杆挤压，连续5分钟。最后一个增强比率或断点可作为社会动机的定量量度。对于第二个范例，叔EST小鼠进行了培训，以获得无论是食物奖励或社会报酬左右杠杆压力机之间的区分。小鼠奖励每个相应杆的每3印刷机。食品和社会奖励的数量可以比作为放置在每一个奖励值的测量。每个奖励类型的比例也可小鼠品系之间比较，并在该比率的变化可以测试会话中进行监测，以测量饱食与给定的奖励类型。这两种操作条件反射范式是社会动机自闭症和社会行为的其他疾病的小鼠模型的量化是非常有用的。

此协议已被用于亲社会C57BL / 6J系小鼠品系与已经先前报告，以显示BTBR近交小鼠品系比较减少在社会行为10,18。它也被用于社会动机在假设已经增加或减少社会动机不同基因敲除小鼠品系的特征。以前发表的结果进行比较的C57BL / 6J和BTBR近交小鼠品系示于图1中 。这些结果表明相比于C57BL / 6J小鼠降低社会动机BTBR小鼠。韦伦比较模式也表现出减少食物动机BTBR小鼠暗示的动机行为这株（ 图1B）全面下降。 图2A呈现在C57BL / 6背景比较株野生型的兄弟姐妹和杂一些homozygo未公布的初步数据我们兄弟姐妹淘汰赛与减少或缺如蛋白质产物的基因（基因X）假设，以促进社会的动力。 图2B呈现在C57BL / 6背景比较株野生型的兄弟姐妹杂淘汰赛兄弟姐妹从降低蛋白质产品的一些未公布的初步数据一个基因（Y）假设以减少社会的动机。从这些研究的初步数据支持每个相应假说和进一步说明描述的操作性社会动机范式的值。 <img alt="图1" src="/files/ftp_upload/53009/53009fig1.jpg" /> 图1.此前公布的结果从社会动机和价比较范式。 （一）单独圈养（IH）B6小鼠，群养（GH）B6小鼠，和群养小鼠BTBR跨越最后10天测试的平均断点的社会动的任务。有共有9各组小鼠的。单独和群养B6小鼠进行的类似，但有群养B6和BTBR小鼠（T = 2.741，DF = 16，P = 0.015）之间的差异显著（B）食物奖励和社会奖励的平均数该群养B6和BTBR小鼠跨越价比较范式的最后10届。两个鼠标群体获得的不是社会的回报显著更多的食物奖励（BTBR:T = 3.551，DF = 8，P = 0.007; B6:T = 9.478，DF = 8，P &lt;0.001）。然而，BTBR小鼠获得比B6小鼠显著较少食物奖励和也最少数量的社会奖励（叔= 3.321，自由度= 16，p值= 0.004）。图修改从参考18。 <img alt="图2" src="/files/ftp_upload/53009/53009fig2.jpg" /> 从利用的社会动范式未发表的研究图2代表性的结果。（A）平均断点（最后钢筋比）达到之前将小鼠停止杆挤压5分钟。用于基因的X，共有12个WT，7 HET和6 KO小鼠中的社会动范例进行了测试。方差分析显示基因型（F = 7.18，DF = 2，22，P = 0.004）之间的差异显著。事后杜克HSD试验表明，KO小鼠低于WT对照显著进行。（B）对于基因Y，共8 HET和6 WT小鼠进行了测试。独立样本t检验显示基因型之间的差异显著（T = 2.26，DF = 8.97，P = 0.05）。 *表示从WT小鼠显著差异在0.05 Alpha级别。

Watch this Scientific Journal Video about Quantifying Social Motivation in Mice Using Operant Conditioning at JoVE.com

Quantifying Social Motivation in Mice Using Operant Conditioning

This article describes a new protocol for the quantitative measurement of social motivation in mice using operant conditioning for a social reward. The protocol is useful for the measurement of social motivation in mouse models of autism and other disorders of social behavior.

量化的社会动机小鼠使用操作条件反射

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered ...

quantifying-social-motivation-in-mice-using-operant-conditioning

Research

JoVE Journal

Behavior

17.9K 次观看.  Azusa Pacific University. This article describes a new protocol for the quantitative measurement of social motivation in mice using operant conditioning for a social reward. The protocol is useful for the measurement of social motivation in mouse models of autism and other disorders of social behavior. 

视频: Quantifying Social Motivation in Mice Using Operant Conditioning

Contextual and Cued Fear Conditioning Test Using a Video Analyzing System in Mice

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association between environmental cues and aversive experiences. In this test, mice are placed into a conditioning chamber and are given parings of a conditioned stimulus (an auditory cue) and an aversive unconditioned stimulus (an electric footshock). After a delay time, the mice are exposed to the same conditioning chamber and a differently shaped chamber with presentation of the auditory cue. Freezing behavior during the test is measured as an index of fear memory. To analyze the behavior automatically, we have developed a video analyzing system using the ImageFZ application software program, which is available as a free download at http://www.mouse-phenotype.org/. Here, to show the details of our protocol, we demonstrate our procedure for the contextual and cued fear conditioning test in C57BL/6J mice using the ImageFZ system. In addition, we validated our protocol and the video analyzing system performance by comparing freezing time measured by the ImageFZ system or a photobeam-based computer measurement system with that scored by a human observer. As shown in our representative results, the data obtained by ImageFZ were similar to those analyzed by a human observer, indicating that the behavioral analysis using the ImageFZ system is highly reliable. The present movie article provides detailed information regarding the test procedures and will promote understanding of the experimental situation.

This article presents a protocol for a contextual and cued fear conditioning test using a video analyzing system to assess fear learning and memory in mice.

背景和线索恐惧制约试验小鼠中使用视频分析系统

The contextual and cued fear conditioning test is one of the behavioral tests that assesses the ability of mice to learn and remember an association ...

科研

行为学

Trace Fear Conditioning in Mice

In this experiment we present a technique to measure learning and memory. In the trace fear conditioning protocol presented here there are five pairings between a neutral stimulus and an unconditioned stimulus. There is a 20 sec trace period that separates each conditioning trial. On the following day freezing is measured during presentation of the conditioned stimulus (CS) and trace period. On the third day there is an 8 min test to measure contextual memory. The representative results are from mice that were presented with the aversive unconditioned stimulus (shock) compared to mice that received the tone presentations without the unconditioned stimulus. Trace fear conditioning has been successfully used to detect subtle learning and memory deficits and enhancements in mice that are not found with other fear conditioning methods. This type of fear conditioning is believed to be dependent upon connections between the medial prefrontal cortex and the hippocampus. One current controversy is whether this method is believed to be amygdala-independent. Therefore, other fear conditioning testing is needed to examine amygdala-dependent learning and memory effects, such as through the delay fear conditioning.

In the following experiment we describe a protocol for trace fear conditioning in mice. This type of associative memory includes a trace period that separates the neutral stimulus and the unconditioned stimulus.

跟踪恐惧条件小鼠

In this experiment we present a technique to measure learning and memory. In the trace fear conditioning protocol presented here there are five pairings ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

操作性程序，以评估大鼠的行为灵活性

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

修改后的孔板 - 测量行为，认知和社会互动小鼠和大鼠

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

The Social Dimension of Stress: Experimental Manipulations of Social Support and Social Identity in the Trier Social Stress Test

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations supportive behavior of other people as well as positive social relationships can act as powerful resources to cope with stress. In order to study the interplay between these variables, this protocol describes two effective experimental manipulations of social relationships and supportive behavior in the laboratory. In the present article, these two manipulations are implemented in the Trier Social Stress Test (TSST)&#8212;a standard stress induction paradigm in which participants are subjected to a simulated job interview. More precisely, we propose (a) a manipulation of the relationship between different protagonists in the TSST by making a shared social identity salient and (b) a manipulation of the behavior of the TSST-selection committee, which acts either supportively or unsupportively. These two experimental manipulations are designed in a modular fashion and can be applied independently of each other but can also be combined. Moreover, these two manipulations can also be integrated into other stress protocols and into other standardized social interactions such as trust games, negotiation tasks, or other group tasks.

Previous research on the social dimension of stress has focused on two important variables: social identity and social support. This protocol introduces an effective experimental manipulation of these two social variables and describes their implementation in a standard stress induction paradigm (Trier Social Stress Test).

应力的社会问题:社会支持和社会认同的特里尔社会的实验操作压力测试

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations ...

Whisker-signaled Eyeblink Classical Conditioning in Head-fixed Mice

Eyeblink conditioning is a common paradigm for investigating the neural mechanisms underlying learning and memory. To better utilize the extensive repertoire of scientific techniques available to study learning and memory at the cellular level, it is ideal to have a stable cranial platform. Because mice do not readily tolerate restraint, they are usually trained while moving about freely in a chamber. Conditioned stimulus (CS) and unconditioned stimulus (US) information are delivered and eyeblink responses recorded via a tether connected to the mouse's head. In the head-fixed apparatus presented here, mice are allowed to run as they desire while their heads are secured to facilitate experimentation. Reliable conditioning of the eyeblink response is obtained with this training apparatus, which allows for the delivery of whisker stimulation as the CS, a periorbital electrical shock as the US, and analysis of electromyographic (EMG) activity from the eyelid to detect blink responses.

The preparation presented here for whisker-signaled eyeblink conditioning in head-fixed mice precisely stimulates specific whiskers while allowing mice to ambulate on a cylindrical treadmill. A whisker stimulation conditioned stimulus (CS) paired with a periorbital shock unconditioned stimulus (US) results in reliable associative learning on this apparatus.

在头固定小鼠胡须信号眨眼经典条件反射

Eyeblink conditioning is a common paradigm for investigating the neural mechanisms underlying learning and memory. To better utilize the extensive ...

Examining Recall Memory in Infancy and Early Childhood Using the Elicited Imitation Paradigm

The ability to recall the past allows us to report on details of previous experiences, from the everyday to the significant. Because recall memory is commonly assessed using verbal report paradigms in adults, studying the development of this ability in preverbal infants and children proved challenging. Over the past 30 years, researchers have developed a non-verbal means of assessing recall memory known as the elicited or deferred imitation paradigm. In one variant of the procedure, participants are presented with novel three-dimensional stimuli for a brief baseline period before a researcher demonstrates a series of actions that culminate in an end- or goal-state. The participant is allowed to imitate the demonstrated actions immediately, after a delay, or both. Recall performance is then compared to baseline or to performance on novel control sequences presented at the same session; memory can be assessed for the individual target actions and the order in which they were completed. This procedure is an accepted analogue to the verbal report techniques used with adults, and it has served to establish a solid foundation of the nature of recall memory in infancy and early childhood. In addition, the elicited or deferred imitation procedure has been modified and adapted to answer questions relevant to other aspects of cognitive functioning. The broad utility and application of imitation paradigms is discussed, along with limitations of the approach and directions for future research.

The elicited imitation procedure was established to examine the development of recall memory in infancy and early childhood. This procedure has been widely used to establish a solid foundation of the nature of recall memory in infancy and early childhood.

使用仿引起范式检查召回内存在婴幼儿时期

The ability to recall the past allows us to report on details of previous experiences, from the everyday to the significant. Because recall memory is ...

An Operant Intra-/Extra-dimensional Set-shift Task for Mice

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric diseases. The most widely used neuropsychological tests for the evaluation of attentional set-shifting in human subjects are the Wisconsin Card Sorting Test (WCST) and the CANTAB Intra-/Extra-dimensional set shift task (ID/ED). These tasks have proven clinical relevance and have been modified and successfully adapted for research in animal models. However, currently available tasks for rodents present several limitations, mainly due to their manual-based testing procedures, which are hampering translational advances in psychiatric medicine. To overcome these limitations and to better mimic the original version in primates, we present the development of a novel operant-based two-chamber ID/ED "Operon" task for rodents. We demonstrated the effectiveness of this novel task to measure different facets of cognitive flexibility in mice including attentional set formation and shifting, and reversal learning. Moreover, we show the high flexibility of this task in which three different perceptual dimensions can be manipulated with a high number of stimuli cues for each dimension. This novel ID/ED Operon task can be an effective preclinical tool for drug testing and/or large genetic screening relevant to the study of executive dysfunction and cognitive symptoms found in psychiatric disorders.

Attentional set-shifting cognitive abnormalities are a core feature of many psychiatric diseases. Here, we present the development of a novel automatic system for the effective study of attentional set-shifting abilities, executive functions and other cognitive abilities in mice with high translational validity to human studies.

一个操作性内/外维特班任务的小鼠

Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric ...

Operant Conditioning Task to Measure Song Preference in Zebra Finches

An operant conditioning paradigm is used to test the song preference of female zebra finches. Finches are placed in a two-chambered cage with a connecting opening and indicate their preference for a song by landing on a perch within each chamber. By interrupting the infrared beam from a photoelectric sensor above each perch, the bird activates the playback of a song through a speaker located on each side of the cage. Freely available software is used to trigger the song playback from each perch. To determine the song preference of each animal, her chamber preference is first identified by triggering no song playback when she lands on each perch. This chamber preference is then compared to her song preference. A minimum activity threshold is set to ensure the preference is real. Using this method, we show that paired females prefer the song of their partner. This method was used to understand the contribution of dopamine to the formation and maintenance of song preference.

We describe a technique to evaluate song preference in zebra finches. Females are placed in a two-chambered cage and song preference is measured by the number of times she triggers the playback of one song by landing on a perch within one chamber, compared with triggering a different song in the second chamber. Perch landings are counted using infrared sensors.

操作调节任务，以测量斑马芬奇中的歌曲首选项

An operant conditioning paradigm is used to test the song preference of female zebra finches. Finches are placed in a two-chambered cage with a connecting ...

Tracking Rats in Operant Conditioning Chambers Using a Versatile Homemade Video Camera and DeepLabCut

Operant conditioning chambers are used to perform a wide range of behavioral tests in the field of neuroscience. The recorded data is typically based on the triggering of lever and nose-poke sensors present inside the chambers. While this provides a detailed view of when and how animals perform certain responses, it cannot be used to evaluate behaviors that do not trigger any sensors. As such, assessing how animals position themselves and move inside the chamber is rarely possible. To obtain this information, researchers generally have to record and analyze videos. Manufacturers of operant conditioning chambers can typically supply their customers with high-quality camera setups. However, these can be very costly and do not necessarily fit chambers from other manufacturers or other behavioral test setups. The current protocol describes how to build an inexpensive and versatile video camera using hobby electronics components. It further describes how to use the image analysis software package DeepLabCut to track the status of a strong light signal, as well as the position of a rat, in videos gathered from an operant conditioning chamber. The former is a great aid when selecting short segments of interest in videos that cover entire test sessions, and the latter enables analysis of parameters that cannot be obtained from the data logs produced by the operant chambers.

This protocol describes how to build a small and versatile video camera, and how to use videos obtained from it to train a neural network to track the position of an animal inside operant conditioning chambers. This is a valuable complement to standard analyses of data logs obtained from operant conditioning tests.

使用多功能自制摄像机和 DeepLabCut 跟踪操作调节室中的大鼠

Operant conditioning chambers are used to perform a wide range of behavioral tests in the field of neuroscience. The recorded data is typically based on ...