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评估小鼠的打洞、筑巢和贮藏行为。

Assessing burrowing, nest construction, and hoarding in mice.

作者信息

Deacon Robert

机构信息

Department of Experimental Psychology, University of Oxford.

出版信息

J Vis Exp. 2012 Jan 5(59):e2607. doi: 10.3791/2607.

Abstract

Deterioration in the ability to perform "Activities of daily living" (ADL) is an early sign of Alzheimer's disease (AD). Preclinical behavioural screening of possible treatments for AD currently largely focuses on cognitive testing, which frequently demands expensive equipment and lots of experimenter time. However, human episodic memory (the most severely affected aspect of memory in AD) is different to rodent memory, which seems to be largely non-episodic. Therefore the present ways of screening for new AD treatments for AD in rodents are intrinsically unlikely to succeed. A new approach to preclinical screening would be to characterise the ADL of mice. Fortuitously, several such assays have recently been developed at Oxford, and here the three most sensitive and well-characterised are presented. Burrowing was first developed in Oxford. It evolved from a need to develop a mouse hoarding paradigm. Most published rodent hoarding paradigms required a distant food source to be linked to the home cage by a connecting passage. This would involve modifying the home cage as well as making a mouse-proof connecting passage and food source. So it was considered whether it would be possible to put the food source inside the cage. It was found that if a container was placed on the floor it was emptied by the next morning., The food pellets were, however, simply deposited in a heap at the container entrance, rather than placed in a discrete place away from the container, as might be expected if the mice were truly hoarding them. Close inspection showed that the mice were performing digging ("burrowing") movements, not carrying the pellets in their mouths to a selected place as they would if truly hoarding them. Food pellets are not an essential substrate for burrowing; mice will empty tubes filled with sand, gravel, even soiled bedding from their own cage. Moreover, they will empty a full tube even if an empty one is placed next to it. Several nesting protocols exist in the literature. The present Oxford one simplifies the procedure and has a well-defined scoring system for nest quality. A hoarding paradigm was later developed in which the mice, rather than hoarding back to the real home cage, were adapted to living in the "home base" of a hoarding apparatus. This home base was connected to a tube made of wire mesh, the distal end of which contained the food source. This arrangement proved to yield good hoarding behaviour, as long as the mice were adapted to living in the "home base" during the day and only allowed to enter the hoarding tube at night.

摘要

“日常生活活动”(ADL)能力的下降是阿尔茨海默病(AD)的早期迹象。目前,针对AD可能治疗方法的临床前行为筛查主要集中在认知测试上,这通常需要昂贵的设备和大量实验人员的时间。然而,人类情景记忆(AD中受影响最严重的记忆方面)与啮齿动物记忆不同,后者似乎主要是非情景性的。因此,目前在啮齿动物中筛选AD新治疗方法的方式本质上不太可能成功。临床前筛查的一种新方法是对小鼠的ADL进行表征。幸运的是,牛津大学最近开发了几种这样的试验方法,这里介绍三种最敏感且特征明确的方法。挖掘行为试验最早在牛津大学开发。它源于开发一种小鼠囤积范式的需求。大多数已发表的啮齿动物囤积范式要求通过连接通道将远处的食物源与饲养笼相连。这将涉及改造饲养笼以及制作防鼠的连接通道和食物源。所以人们考虑是否有可能将食物源放在笼子里。结果发现,如果在笼子地板上放置一个容器,到第二天早上它就会被清空。然而,食物颗粒只是简单地堆积在容器入口处成一堆,而不是像如果小鼠真的在囤积它们可能预期的那样被放置在远离容器的一个单独位置。仔细观察表明,小鼠是在进行挖掘(“打洞”)动作,而不是像真的在囤积时那样用嘴把颗粒叼到选定的地方。食物颗粒不是挖掘行为的必需底物;小鼠会清空装满沙子、砾石甚至它们自己笼子里脏垫料的管子。此外,即使旁边放着一个空管子,它们也会清空一个满管子。文献中有几种筑巢方案。目前牛津大学的这种方案简化了程序,并且有一个明确的巢穴质量评分系统。后来开发了一种囤积范式,其中小鼠不是囤积回真正的饲养笼,而是适应生活在一个囤积装置的“大本营”中。这个大本营与一个金属丝网制成的管子相连,管子的远端装有食物源。事实证明,只要小鼠白天适应生活在“大本营”中,并且只在晚上被允许进入囤积管子,这种安排就能产生良好的囤积行为。

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