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><tbody><tr><td>Modular Shuttle Box</td><td>Med Associates Inc.</td><td>ENV-010MC</td><td></td></tr><tr><td>Auto-Guillotine Door&amp;nbsp;</td><td>Med Associates Inc.</td><td>ENV-010B</td><td></td></tr><tr><td>Mouse Levers&amp;nbsp;</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&amp;nbsp;</td><td>Med Associates Inc.</td><td>ENV-253C</td><td></td></tr><tr><td>Melamine Sound-Attenuating Cubicle&amp;nbsp;</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&amp;nbsp;</td><td></td></tr><tr><td>Microsoft Lifecam Camera&amp;nbsp;</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.&amp;nbsp;</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 for each reward per mouse. We always purchase the same brand for better consistency.&amp;nbsp;</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.&amp;nbsp;</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

Universidad San Sebastian

Research

JoVE Journal

Behavior

18.0K 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

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

Operant Sensation Seeking in the Mouse

Operant methods are powerful behavioral tools for the study of motivated behavior. These 'self-administration' methods have been used extensively in drug addiction research due to their high construct validity. Operant studies provide researchers a tool for preclinical investigation of several aspects of the addiction process. For example, mechanisms of acute reinforcement (both drug and non-drug) can be tested using pharmacological or genetic tools to determine the ability of a molecular target to influence self-administration behavior1-6. Additionally, drug or food seeking behaviors can be studied in the absence of the primary reinforcer, and the ability of pharmacological compounds to disrupt this process is a preclinical model for discovery of molecular targets and compounds that may be useful for the treatment of addiction3,7-9. One problem with performing intravenous drug self-administration studies in the mouse is the technical difficulty of maintaining catheter patency. Attrition rates in these experiments are high and can reach 40% or higher10-15. Another general problem with drug self-administration is discerning which pharmacologically-induced effects of the reinforcer produce specific behaviors. For example, measurement of the reinforcing and neurological effects of psychostimulants can be confounded by their psychomotor effects. Operant methods using food reinforcement can avoid these pitfalls, although their utility in studying drug addiction is limited by the fact that some manipulations that alter drug self-administration have a minimal impact on food self-administration. For example, mesolimbic dopamine lesion or knockout of the D1 dopamine receptor reduce cocaine self-administration without having a significant impact on food self-administration 12,16. 
Sensory stimuli have been described for their ability to support operant responding as primary reinforcers (i.e. not conditioned reinforcers)17-22. Auditory and visual stimuli are self-administered by several species18,21,23, although surprisingly little is known about the neural mechanisms underlying this reinforcement. The operant sensation seeking (OSS) model is a robust model for obtaining sensory self-administration in the mouse, allowing the study of neural mechanisms important in sensory reinforcement24. An additional advantage of OSS is the ability to screen mutant mice for differences in operant behavior that may be relevant to addiction. We have reported that dopamine D1 receptor knockout mice, previously shown to be deficient in psychostimulant self-administration, also fail to acquire OSS24. This is a unique finding in that these mice are capable of learning an operant task when food is used as a reinforcer. While operant studies using food reinforcement can be useful in the study of general motivated behavior and the mechanisms underlying food reinforcement, as mentioned above, these studies are limited in their application to studying molecular mechanisms of drug addiction. Thus, there may be similar neural substrates mediating sensory and psychostimulant reinforcement that are distinct from food reinforcement, which would make OSS a particularly attractive model for the study of drug addiction processes. The degree of overlap between other molecular targets of OSS and drug reinforcers is unclear, but is a topic that we are currently pursuing. While some aspects of addiction such as resistance to extinction may be observed with OSS, we have found that escalation 25 is not observed in this model24. Interestingly, escalation of intake and some other aspects of addiction are observed with self-administration of sucrose26. Thus, when non-drug operant procedures are desired to study addiction-related processes, food or sensory reinforcers can be chosen to best fit the particular question being asked. 
In conclusion, both food self-administration and OSS in the mouse have the advantage of not requiring an intravenous catheter, which allows a higher throughput means to study the effects of pharmacological or genetic manipulation of neural targets involved in motivation. While operant testing using food as a reinforcer is particularly useful in the study of the regulation of food intake, OSS is particularly apt for studying reinforcement mechanisms of sensory stimuli and may have broad applicability to novelty seeking and addiction.

In this protocol we describe a method of operant learning using sensory stimuli as a reinforcer in the mouse. It requires no prior training or food restriction, and it allows the study of motivated behavior without the use of a pharmacological or natural reinforcer such as food.

在鼠标的操作性感觉寻求

Operant methods are powerful behavioral tools for the study of motivated behavior.  These 'self-administration' methods have been used extensively in drug ...

神经科学

Experimental Assessment of Mouse Sociability Using an Automated Image Processing Approach

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the test mouse is placed in a standardized apparatus and relevant behaviors are assessed in three different sessions (called session I, II, and III).
The apparatus has three compartments (see Figure 1), the left and right compartments contain an inverted cup which can house a mouse (called &#34;stimulus mouse&#34;).
In session I, the test mouse is placed in the cage and its mobility is characterized by the number of transitions made between compartments. In session II, a stimulus mouse is placed under one of the inverted cups and the sociability of the test mouse is quantified by the amounts of time it spends near the cup containing the enclosed stimulus mouse vs. the empty inverted cup. In session III, the inverted cups are removed and both mice interact freely. The sociability of the test mouse in session III is quantified by the number of social approaches it makes toward the stimulus mouse and by the number of times it avoids a social approach by the stimulus mouse.
The automated evaluation of the movie detects the nose of the test mouse, which allows the determination of all described sociability measures in session I and II (in session III, approaches are identified automatically but classified manually). To find the nose, the image of an empty cage is digitally subtracted from each frame of the movie and the resulting image is binarized to identify the mouse pixels. The mouse tail is automatically removed and the two most distant points of the remaining mouse are determined; these are close to nose and base of tail. By analyzing the motion of the mouse and using continuity arguments, the nose is identified.
<img alt="Figure 1" src="/files/ftp_upload/52508/52508fig1.jpg" /> 
Figure 1. Assessment of Sociability During 3 sessions. Session I (top): Acclimation of test mouse to the cage. Session II (middle): Test mouse moving freely in the cage while the stimulus mouse is enclosed in an inverted cup. Session III (bottom): Both test mouse and stimulus mouse are allowed to move freely and interact with each other.

This protocol describes a method to quantify mouse sociability. Mice are videotaped as they move and interact in a special cage. Movie processing allows for the automated quantification of sociability with excellent accuracy and reliability.

使用自动图像处理方法鼠标社交性的实验评估

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the ...

Assessment of Social Interaction Behaviors

Social interactions are a fundamental and adaptive component of the biology of numerous species. Social recognition is critical for the structure and stability of the networks and relationships that define societies. For animals, such as mice, recognition of conspecifics may be important for maintaining social hierarchy and for mate choice 1.
A variety of neuropsychiatric disorders are characterized by disruptions in social behavior and social recognition, including depression, autism spectrum disorders, bipolar disorders, obsessive-compulsive disorders, and schizophrenia. Studies of humans as well as animal models (e.g., Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, Rattus norvegicus) have identified genes involved in the regulation of social behavior 2. To assess sociability in animal models, several behavioral tests have been developed (reviewed in 3). Integrative research using animal models and appropriate tests for social behavior may lead to the development of improved treatments for social psychopathologies.
The three-chamber paradigm test known as Crawley's sociability and preference for social novelty protocol has been successfully employed to study social affiliation and social memory in several inbred and mutant mouse lines (e.g. 4-7). The main principle of this test is based on the free choice by a subject mouse to spend time in any of three box's compartments during two experimental sessions, including indirect contact with one or two mice with which it is unfamiliar. To quantitate social tendencies of the experimental mouse, the main tasks are to measure a) the time spent with a novel conspecific and b) preference for a novel vs. a familiar conspecific. Thus, the experimental design of this test allows evaluation of two critical but distinguishable aspects of social behavior, such as social affiliation/motivation, as well as social memory and novelty. "Sociability" in this case is defined as propensity to spend time with another mouse, as compared to time spent alone in an identical but empty chamber 7. "Preference for social novelty" is defined as propensity to spend time with a previously unencountered mouse rather than with a familiar mouse 7. This test provides robust results, which then must be carefully analyzed, interpreted and supported/confirmed by alternative sociability tests. In addition to specific applications, Crawley's sociability test can be included as an important component of general behavioral screen of mutant mice.

Here we describe a detailed protocol for examination of sociability in mice by using Crawley's sociability and preference for social novelty test. We describe the advantages and possible applications for this procedure, including critical details important for correct interpretation of the results.

社会交往行为的评估

Social interactions are a fundamental and adaptive component of the biology of numerous species. Social recognition is critical for the structure and ...

Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior

Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as appropriate models, partly because the response to behaviorally relevant stimuli and the circuitry parsing stimulus-action outcomes is astonishingly similar between humans and rodents. In studying molecular substrates of complex behaviors, the microinjection of reagents that modify, augment, or silence specific systems is an invaluable technique. However, it is crucial that the microinjection site is precisely targeted in order to aid interpretation of the results. We present a method for the manufacture of surgical implements and microinjection needles that enables accurate microinjection and unlimited customizability with minimal cost. Importantly, this technique can be successfully completed in awake rodents if conducted in conjunction with other JoVE articles that covered requisite surgical procedures. Additionally, there are many behavioral paradigms that are well suited for measuring motivation. The progressive ratio is a commonly used method that quantifies the efficacy of a reinforcer to maintain responding despite an (often exponentially) increasing work requirement. This assay is sensitive to reinforcer magnitude and pharmacological manipulations, which allows reinforcing efficacy and/ or motivation to be determined. We also present a straightforward approach to program operant software to accommodate a progressive ratio reinforcement schedule.

Rodents are an appropriate model to investigate the molecular substrates of behavior and complex psychiatric disorders. Brain microinjection in awake rodents can be used to elucidate disease substrates. An efficient and customizable brain microinjection method as well as the execution of an operant paradigm that quantifies motivation is presented.

啮齿动物脑显微注射学习动机行为的分子基板

Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as ...

Introducing Clicker Training as a Cognitive Enrichment for Laboratory Mice

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous research determined a profound impact of gentle handling protocols on the well-being of laboratory mice. By introducing clicker training to the keeping of mice, not only do we promote the amicable treatment of mice, but we also enable them to experience cognitive enrichment. Clicker training is a form of positive reinforcement training using a conditioned secondary reinforcer, the "click" sound of a clicker, which serves as a time bridge between the strengthened behavior and an upcoming reward. The effective implementation of the clicker training protocol with a cohort of 12 BALB/c inbred mice of each sex proved to be uncomplicated. The mice learned rather quickly when challenged with tasks of the clicker training protocol, and almost all trained mice overcame the challenges they were given (100% of female mice and 83% of male mice). This study has identified that clicker training for mice strongly correlates with reduced fear in the mice during human-mice interactions, as shown by reduced anxiety-related behaviors (e.g., defecation, vocalization, and urination) and fewer depression-like behaviors (e.g., floating). By developing a reliable protocol that can be easily integrated into the daily routine of the keeping of laboratory mice, the lifetime experience of welfare in the mice can be improved substantially.

The development of new refinement strategies for laboratory mice is a challenging task that contributes towards fulfilling the 3R principle. This protocol introduces clicker training as a cognitive enrichment program for laboratory mice.

引进响片训练为实验室老鼠认知富集

Establishing new refinement strategies in laboratory animal science is a central goal in fulfilling the requirements of Directive 2010/63/EU. Previous ...

Analyzing Spatial Learning and Prosocial Behavior in Mice Using the Barnes Maze and Damsel-in-Distress Paradigms

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. The Barnes maze can also assess other mouse behaviors, such as general motivation to escape from the maze platform and exploratory behavior. The Barnes maze can measure whether a genetic mutation or environmental variable can impact the acquisition and retention of spatial memories, as well as provide information about the search strategy employed by the mice. Here we use the Barnes maze to detect a memory deficit in adult mice following a single developmental ethanol exposure event. The newly described Damsel-in-Distress paradigm exposes a male mouse to a female mouse trapped in a chamber in the open center field of the arena. It provides an opportunity for the mouse to socially respond to the trapped female and exhibit prosocial behavior. The Damsel-in-Distress paradigm can also be used to examine mouse behavior in a novel arena and measure locomotor activity. Both the Barnes Maze and the Damsel-in-Distress protocols require minimal financial investment and most aspects of the tests can be constructed from common lab supplies. These flexible and accessible tools can also be used to detect behavioral changes over the course of development.

This protocol measures spatial learning and memory using the Barnes maze. A novel Damsel-in-Distress paradigm is used to assess locomotor activity and prosocial behavior in mice.

利用巴恩斯迷宫和困境中的破坏范式分析小鼠的空间学习和社会行为

The Barnes maze is a reliable measure of spatial learning and memory that does not require food restriction or exposure to extremely stressful stimuli. ...

A System for Tracking the Dynamics of Social Preference Behavior in Small Rodents

Exploring the neurobiological mechanisms of social behavior requires behavioral tests that can be applied to animal models in an unbiased and observer-independent manner. Since the beginning of the millennium, the three-chamber test has been widely used as a standard paradigm to evaluate sociability (social preference) and social novelty preference in small rodents. However, this test suffers from multiple limitations, including its dependence on spatial navigation and negligence of behavioral dynamics. Presented and validated here is a novel experimental system that offers an alternative to the three-chamber test, while also solving some of its caveats. The system requires a simple and affordable experimental apparatus and publicly available open-source analysis system, which automatically measures and analyzes multiple behavioral parameters at individual and population levels. It allows detailed analysis of the behavioral dynamics of small rodents during any social discrimination test. We demonstrate the efficiency of the system in analyzing the dynamics of social behavior during the social preference and social novelty preference tests as performed by adult male mice and rats. Moreover, we validate the ability of the system to reveal modified dynamics of social behavior in rodents following manipulations such as whisker trimming. Thus, the system allows for rigorous investigation of social behavior and dynamics in small rodent models and supports more accurate comparisons between strains, conditions, and treatments.

Described here is a novel automated experimental system that offers an alternative to the three-chamber test and also solves several caveats. This system supplies multiple behavioral parameters that enable rigorous analysis of small rodent behavioral dynamics during the social preference and social novelty preference tests.

跟踪小啮齿动物社会偏好行为动态的系统

Exploring the neurobiological mechanisms of social behavior requires behavioral tests that can be applied to animal models in an unbiased and ...

<meta charset="utf8"></head><body>小鼠模型中自闭症谱系障碍的行为检测

Strategies for Assessing Autistic-Like Behaviors in Mice

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).

<meta charset="utf8"></head><body>评估小鼠自闭症样行为的策略

Rodent models are valuable tools for studying core behaviors related to autism spectrum disorder (ASD). In this article, we expound on two behavioral tests for modeling the core features of ASD in mice: self-grooming, which assesses repetitive behavior, and the three-chamber social interaction test, which documents social impairments.

评估小鼠自闭症样行为的策略

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social ...

量化的社会动机小鼠使用操作条件反射

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此视频中的章节

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

在鼠标的操作性感觉寻求

使用自动图像处理方法鼠标社交性的实验评估

社会交往行为的评估

啮齿动物脑显微注射学习动机行为的分子基板

引进响片训练为实验室老鼠认知富集

利用巴恩斯迷宫和困境中的破坏范式分析小鼠的空间学习和社会行为

跟踪小啮齿动物社会偏好行为动态的系统

评估小鼠自闭症样行为的策略

评估小鼠自闭症样行为的策略