新对象的探索在小鼠电位测定高阶重复的行为
Summary
Higher order restricted, repetitive behaviors (RRBs) disrupt the lives of affected individuals. These behaviors are challenging to model in rodents, making basic biomedical research into potential treatments or interventions for RRBs difficult. Here we describe novel object exploration as a potential assay for higher order RRBs in mice.
Abstract
Restricted, repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD) and disrupt the lives of affected individuals. RRBs are commonly split into lower-order and higher-order components, with lower order RRBs consisting of motor stereotypies and higher order RRBs consisting of perseverative and sequencing behaviors. Higher order RRBs are challenging to model in mice. Current assays for RRBs in mice focus primarily on the lower order components, making basic biomedical research into potential treatments or interventions for higher-order RRBs difficult. Here we describe a new assay, novel object exploration. This assay uses a basic open-field arena with four novel objects placed around the perimeter. The test mouse is allowed to freely explore the arena and the order in which the mouse investigates the novel objects is recorded. From these data, patterned sequences of exploration can be identified, as can the most preferred object for each mouse. The representative data shared here and past results using the novel object exploration assay illustrate that inbred mouse strains do demonstrate different behavior in this assay and that strains with elevated lower order RRBs also show elevated patterned behavior. As such, the novel object exploration assay appears to possess good face validity for higher order RRBs in humans and may be a valuable assay for future studies investigating novel therapeutics for ASD.
Introduction
自闭症谱系障碍（ASD）是一个由三个核心症状的神经发育障碍：社会障碍，难以通过语言沟通，和重复图案的行为1。自2000年以来，谁被诊断患有自闭症的个体数从1 150十年2跨度提高到1 68。虽然该病症的发生率不断增加，这种疾病的原因尚不清楚。目前已在努力确定的核心和ASD的相关症状适当的鼠标模型，这些模型可能会导致ASD的基本症状和原因的认识增加上升。有迹象表明，似乎显示与表面效度的行为ASD的核心症状，包括重复的行为3多个近交系小鼠品系。
限定，重复的行为（RRBs）是一些精神障碍，例如ASD的核心症状。RRBs可以与病症4的严重性增加，并且可以极大地破坏受影响的个体的生活方式。 RRBs通常分为两类，低阶重复行为，其在人类中包括诸如摆动和手拍打行动;和高阶重复行为，其由严格遵守的常规和电阻变化5-8。
低阶重复行为已被广泛研究中，他们表现为运动癖，其可在实验室设置9容易地观察到啮齿动物。这些行为似乎在人类的好脸色有效性RRBs，和巨大潜力的构想效度，以及10。对于低阶RRBs的存在测试可以通过鼠标活动的视频监控完成，以研究这些电机的刻板11的较量和持续时间。高阶重复的行为姿势基础生物医学重新挑战利用搜索啮齿动物，因为这些RRBs不是通过简单的观察是很容易识别。由于在确定这些行为困难，存在高阶重复行为更少建立测定。传统上，高阶RRBs已经在使用迷津，其中试验动物被训练逃脱到达能力啮齿动物进行测量。然后逃逸位置被切换和重新学习的逃逸位置所需试验次数被记录12。这些测定法是不理想的，因为它们需要一个长的训练周期，经常诱发焦虑，并可能导致高度可变的结果。空穴板勘探也被用来量化高阶RRBs 13,14。这种方法不需要延长培训课程，但依靠食物的动机和/或嗅觉辨别。试验高阶RRBs是不引起焦虑或者需要训练将是一个很好的补充洞板勘查现有剧目 n和目前使用的基于迷宫的测定法。
在C58 / J（C58）近交系小鼠强烈体现了高水平的房间隔缺损，即重复，无目的刻板电机和自我疏导3,11水平升高相关的刻板行为。此外，C58小鼠显示通过高水平的饲养，背翻转和摸索11,14,16的RRBs。该菌株开始在新生儿期早期显示这些行为，并继续整个成年期显示出来。这将是理想的，以便能够测试对于高阶升高RRBs的存在下，以补充存在于该菌株中以及其它小鼠品系的证据充分的低阶RRBs。这里所描述的新颖的对象勘探测定为研究人员提供能够同时观察低阶和高阶RRBs，因为它给测量图案化的行为以及重复电动机的刻板的能力的机会。
e_content“>使用新物体勘探作为高阶重复行为的测定通过Pearson 等人开发的。17，这新的评估是行之有效的旷场试验18-21中，并添加四种新型的对象到扩展舞台。小鼠允许自由调查这些陌生的对象的数量和对象的调查的顺序被跟踪然后，进行了分析模式的存在的对象的调查，以显示所述对象之间的图案化的调查升高号码BTBR小鼠。使用该测定中，小鼠可以在无需学习行为以及去除不必要的刺激显示高阶重复并构图的行为。小说对象勘探诱导高阶RRBs，因为它允许将小鼠通过其天然勘探创建图案和形式的序列。使用该测定允许研究者量化这些高阶RRBs的存在。Pearson 等人 。开发了这个实验，并用它来 测试潜在的高阶重复的行为在BTBR近交系小鼠的存在，用有趣的结果17。我们最近发表的后续研究看C58，C57BL / 6J（C57）和FVB /新泽西州（FVB）菌株的行为，以及更详细的调查潜在混杂变量存在于该测定中，以及可能的统计方法分析数据生成22。
Protocol
Representative Results
Discussion
在这里，我们提出了一个新近开发的分析，可能是与表面效度量化鼠标行为在人类高阶重复的行为非常有用。不同于像巴恩斯或T型迷宫更成熟的试验，这种新的对象探索试验并不需要任何鼠标的训练也不是特别焦虑发人深省。此外，新的物体勘探不需要任何食物或社会刺激，从而允许更专注于感兴趣，RRBs行为，并减少混淆变量倾斜的结果的可能性。此外，不同品系小鼠做证明在该试验中不同行?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
笔者想承认暑期大学生研究计划，学术技术用户组，中心的数字化学习，并在雷德兰兹大学的科学中心。
笔者希望本文献给娄扬戈的记忆。
Materials
| Standard Polycarbonate Rodent Cage (45 x 24 x 20 cm) | Multiple cages are desirable to facilitate testing of multiple mice | ||
| Plastic Opaque Circular Testing Arena (41 cm base diameter) | United States Plastic Corp. | 13931 | Multiple arenas are desirable to facilitate testing of multiple mice |
| Standard Corn-Cob Rodent Bedding | |||
| Novel Object – red monkey | Hasbro, Pawtucket RI | from Barrel of Monkeys | |
| Novel Object – rectangular 2×4 LEGO | |||
| Novel Object – tile | Thinkfun Inc., Alexandria VA | from Toot and Otto | |
| Novel Object – standard white die | |||
| Video Camera | |||
| Behavioral Logging Software – The Observer | Noldus, Wageningen, The Netherlands | other programs may be used | |
| Video Tracking Software – EthoVision | Noldus, Wageningen, The Netherlands | other programs may be used | |
| X-Keys input keyboard | P.I. Engineering, Williamstown MI | 829484 | |
| MacroWorks II | P.I. Engineering, Williamstown MI | ||
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