We would like to dedicate this work to the memory of late Dr. William T. Greenough, a great mentor, a colleague and a friend. This work was supported by NIH/NIAAA grant number AA009838 and NIH/NIGMS COBRE: The Delaware Center for Neuroscience research grant 1P20GM103653 to AYK. We are grateful to the former and current members of Klintsova lab.

伦理声明:以下方案经特拉华大学的机构动物护理和使用委员会（IACUC）。 1.发展曝光（或狂欢般的乙醇暴露的模型） <ol><li>上PD3，确定每只动物的性别和交叉培养任何动物，如果必要保持产仔（8只动物）和性别分布（4-男性:女性4），每个窝内是一致的。 注意:要保持产仔数和性别分布尽可能一致以避免试验的困惑是很重要的。虽然这个协议使用每窝幼仔8（4男4女），另一种垃圾大小和性别分布，可以量身定制试验设计的需要。 </li><li>皮下注入黑墨汁的少量到爪子每窝内识别动物。 </li><li>伪随机地分配窝作为实验（含50％醇的曝光（AE）和50％的假插管控制（SI）的小狗多个）或哺乳控制（SC）（即不进行任何插管，尾部剪裁，或分离的协议从PD 4的动物 - 9除了每日称重和耳打孔）。 <ol><li>为了保持一致性组的大小，分配两倍的实验窝为SC窝。 </li></ol></li><li>称量每个动物然后返回到其家笼。动物称重应在气管插管期间（PD 4 - 9）每天都在发生。 <ol><li>拆除大坝整个垃圾。 </li><li>放置在加热垫的幼崽。 </li><li>记录每个个体小狗的重量。 </li></ol></li><li>上PD4，称量每只动物后计算总共每各动物5.25克/ kg /天的必要醇量（基于小狗重量从步骤1.4）8。 <ol><li>辖醇11.9％的乙醇 - 在奶代用品（体积/体积）。 </li></ol></li><li>上午9点开始，一次删除从母亲一窝的幼崽。 </li><li>辖乙醇的牛奶给每个AE小狗<s补课="外部参照"&gt; 34。 </li><li>假插管每个SI小狗8。 </li><li>重复步骤1.5。通过1.8。每个实验垫料。 </li><li>两个小时的首次剂量下，重复给药过程（步骤1.5至1.8）如属第二酒精剂量。 </li><li>第二酒精剂量（在此高峰每天血液中的酒精含量达到点）后的一个半小时，收集和尾 AE和SI幼仔剪裁为未来的血液酒精含量分析35离心机的血液。 <ol><li>取血60微升。 </li><li>放置血液在1毫升离心管中。血液离心机在1.5 XG 25分钟。 </li><li>仔细收集从离心管上清液血清，并保存为未来的血液酒精含量分析。 </li></ol></li><li>重复使用牛奶而不是乙醇在牛奶定量给料步骤（步骤1.5至1.8），以防止从护理不能在自动曝光营养不足幼崽。 <ol><li>在PD 4除了2小时进行，共有2条补充牛奶的剂量。 </li></ol></li><li> 9 - 对PD 5重复步骤1.4至1.12（除步1.11）。 </li><li>继PD9最后补充牛奶的剂量，耳冲所有幼崽鉴定欧共体笼子里。 <ol><li>协调打孔耳的垃圾数量或标识符一定程度（ 比如 ，一个队列中的奇数窝会得到他们的左耳穿孔而从偶数窝的动物都会得到他们的右耳穿孔）。这将使它更容易识别在欧共体笼子里的动物应该来自不同窝的动物多有相同pawmark模式。 </li></ol></li></ol> 2.断奶<ol><li>在PD 23，房子里所有的动物在笼子里2 - 3。 <ol><li>确保安置在同一个笼子里所有的动物都是同性。 </li><li>包括一个SC，一个SI，以及每笼1 AE动物时可能。 </li><li>最小化笼队友届数在来自同一窝。 </li><li>确保所有的动物都能够访问的食物和水。 </li></ol></li></ol> 3.轮运行<ol><li>在PD30，分配与动物WR笼子的一半。房子这些动物的免费访问连接不锈钢跑轮笼。 <ol><li>确保车轮有一个计数器来评估的总转数。 </li></ol></li><li>打压PD 30和PD 36所有的动物。 </li><li>检查每个车轮的转数在每天上午9点。 </li><li>留在其各自的壳体条件动物12天。 </li></ol> 4.环境的复杂性<ol><li> 09:00之前就对应于PD 42实验动物一天准备EC笼子。 <ol><li>获取30"×18"×36"镀锌钢板笼。 注:笼应该有多个级别，是能够支持多个大鼠的重量，填充有标准床上用品，并有多个位置附加水瓶和食物掌柜。 </li><li>将新的，可变的大小和形状在笼子里的五颜六色的对象。 <ol><li>将6个大玩具在欧共体笼子里。确保每个玩具是3个或更多只与交互同时足够大。 </li><li>将6中的玩具在欧共体笼子里。确保每个玩具是足够大的3 - 4只与同时进行交互。 </li><li>放置的小玩具很多（至少20），在欧共体笼。 </li><li>使用不同的颜色，形状，大小等玩具新奇是这种干预的关键（见讨论）。 </li></ol></li><li>放置食品的两个菜在笼的相对端。 </li><li>放置两瓶水在笼的相对端。 </li></ol></li><li>上午9点42 PD，权衡所有的动物和搬迁WR动物的笼子EC。每个笼子EC应该包含9 - 12只动物。 <ol><li>确保没有动物有两个相同的pawmark和耳双关语通道模式。 </li></ol></li><li>检查所有的食物和水每天。 </li><li>每两天，欧共体笼子里取出玩具和替换它们（根据步骤4.1.2）。 </li><li>每三天，清理笼子EC。 <ol><li>欧共体笼中取出的动物，把他们放在2的临时存放笼 - 3只动物。 </li><li>从笼子的底部卸下所有的床上用品。 </li><li>返回相同的玩具笼子，除非这一天，玩具更换时间表一致（按步骤4.4）。 </li><li>更换所有的食物和水。 </li><li>老鼠装回EC笼子。 </li></ol></li></ol> 5.收集组织注:组织采集（ 例如 ，灌注与多聚甲醛）和存储（ 例如 ，冷冻，石蜡包埋）可与多种方法来进行。下面将说明，用4％多聚甲醛灌注的过程中的0.1M磷酸盐缓冲盐水（PBS中的4％多聚甲醛）解决方案8。 注意:多聚甲醛是致癌物质，还可能引起皮肤刺激，过敏性皮肤反应，或眼睛的伤害。使用适当的眼部/皮肤保护。 <ol><li>公开一个老鼠来一次异氟醚麻醉轻轻动物。 </li><li>腹膜内用2mL / kg的氯胺酮/赛拉嗪混合物（1.5毫升甲苯噻嗪用10mL氯胺酮混合）的注入的大鼠。 注:氯胺酮和赛拉嗪注射混合物结合之前都在库存浓度为100毫克/毫升。 </li><li>一旦大鼠不再响应，灌注用0.1M磷酸盐缓冲盐水的动物;其次是4％多聚甲醛的PBS（pH值= 7.2）（PBS pH值= 7.2）。 </li><li>在PBS中的4％多聚甲醛在4℃下48小时除去脑和存储。 </li><li> 2天后，转移到30％蔗糖溶液加入到在PBS中的4％多聚甲醛在4℃下。 </li></ol>

The authors have nothing to disclose.

在上述协议中，我们展示了一个权宜之计的干预抢救新生儿以下酒精暴露神经解剖的赤字。该干预可作为在其他动物模型中的治疗由于每个干预的组分的鲁棒性。在WR的形式自愿心血管活性已经示出受益几个行为结果38,39和诱发脑区功能性塑料的改变如海马（在40中综述）。这部分是由于在啮齿动物的脑实质生长因子和其他神经保护机?...

在不同的环境中饲养早已知道引起神经健康的各种措施的改变。许多研究着眼于在复杂环境下饲养的开始由钻石和罗森茨韦克（ 如开创性研究的有利影响（EC）， 1，2）和格里诺 （ 例如 ，3，4）。统已被证明对在大脑5，6，7突触和细胞变化不可否认的积极影响。 EC可影响大脑区域的多个包括海马8,9和视觉皮层10，11，腹侧纹状体12，13，以及作为脑宽神经免疫功能（在14中综述）。特别兴趣已经从海马的研究开发，当它被证明EC能够通过树突状可塑性9，13增加了齿状回成人出生的颗粒细胞的成活率。最后这一点已经聚集了极大的兴趣，由于文献表明心血管运动促进成年神经的健康受损的脑都15，16，17，18的越来越多。轮运转（WR）是一个容易实现，已被证明是在神经系统疾病或老化17，19，20的啮齿动物模型有利自愿心血管活性的形式。 WR影响生长因子的表达<html>在中央和周围神经系统21，22，23。 （后来）WR和EC组合成一个"superintervention"（WR-EC）（ 即 ，WR其次是30天乳油12天）提供了在海马成年神经稳健增长，并增加了新增殖细胞8的生存之本，在FASD的动物模型不是由单个组件来实现的效果（见下文）。由于WR-EC的两个组成部分大脑13内影响结构的多样化（WR 22审查，欧盟在24综述），该干预的实施可以很容易地应用到神经系统的两个发育和以后的生活发病模型的啮齿动物模型障碍（ 如新生儿酒精暴露，老化，早期生活压力）。 NT"&gt;在青春期和成年早期阶段（ 即出生后30 - 72）WR-EC的整合可以改善一些胎儿酒精谱系障碍的大鼠模型（FASDs）的负面影响8的研究集合。表明，通过在神经解剖学措施9显示显著赤字暴露于来自日龄（PD）的4醇啮齿类如树突复杂25，小脑发育26,27和神经免疫反应28以及受损学习和存储器29，30的表现，31 。这个时间窗口内酒精暴露即使量减少（ 即 PD 7至9）可导致青少年和成年大鼠32学习记忆障碍，同时一些结构再也看不到签名着的神经解剖减值27。许多这些缺陷的-除了在海马依赖性任务的行为障碍-已减轻暴露于这种WR-EC范例8，33或单独WR 25,31。虽然单独WR已广泛使用的介入，WR-EC的组合尚未在文献中，尽管它维持WR 8的相对短期益处能力利用。本文将在青春期讨论WR-EC干预的实施。尽管这种模式是在出生后早期酒精暴露的环境中使用，它可以引入到各种啮齿动物模型来评估脑电位为脑疾病的模型神经可塑性。

<table border="0" cellpadding="0" cellspacing="0" width="698">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:247px;">Female Time-pregnant Long Evans Rats</td>
			<td style="width:124px;">Envigo (Formerly: Harlan, Inc.)</td>
			<td style="width:136px;"></td>
			<td style="width:191px;">Average litter size is 8-10 pups</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:247px;">Black India Ink</td>
			<td style="width:124px;">Higgins (Chartpak, Inc.)</td>
			<td style="width:136px;">44201</td>
			<td style="width:191px;"></td>
		</tr>
		<tr height="84">
			<td height="84" style="height:84px;width:247px;">Syringes and Injection Needles</td>
			<td style="width:124px;">Becton, Dickinson and Company (BD)</td>
			<td style="width:136px;">Assorted</td>
			<td style="width:191px;">For injection of pawmarking ink, administration of milk-alcohol solution</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:247px;">Ear Punch</td>
			<td style="width:124px;">Kent Scientific Corporation</td>
			<td style="width:136px;">INS750076</td>
			<td style="width:191px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:247px;">Running Wheels</td>
			<td style="width:124px;">Wahmann Labs</td>
			<td style="width:136px;"></td>
			<td style="width:191px;">Wahmann Running Wheel is discontinued. Substitute with&#160; One per cage</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:247px;">EC Cage</td>
			<td style="width:124px;">Martin&#39;s Cages, Inc.</td>
			<td style="width:136px;">R-695</td>
			<td style="width:191px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:247px;">Small EC Toys</td>
			<td style="width:124px;">Assorted</td>
			<td style="width:136px;"></td>
			<td style="width:191px;"></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:247px;">Medium EC Toys</td>
			<td style="width:124px;">Assorted</td>
			<td style="width:136px;"></td>
			<td style="width:191px;">Should be able to fit 1-2 rats inside of/ on top of object</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:247px;">Large EC Toys</td>
			<td style="width:124px;">Assorted</td>
			<td style="width:136px;"></td>
			<td style="width:191px;">Should be able to fit 3 or more rats inside of/on top of object</td>
		</tr>
	</tbody>
</table>

wheel running and environmental complexity as a therapeutic intervention in an animal model of fasd

有氧运动（ 例如 ，车轮运行（WR）在动物研究广泛使用）积极的影响neuroplastic潜在的许多措施在大脑中，如成人神经发生，血管生成，以及在啮齿动物中的神经营养因子表达的速率。该干预也被证明以减轻致畸（ 即发育暴露于醇）和与年龄相关的神经变性的在啮齿类动物中产生的负面影响的行为和神经解剖学方面。环境的复杂性（EC）已经显示出产生在皮质和皮质下结构众多neuroplastic好处，可与车轮运行被耦合以增加成人海马增殖和新的细胞的存活。这两个措施的结合提供了一个坚固的"superintervention"（WR-EC），可在一个范围内的神经系统疾病的啮齿动物模型来实现。我们将讨论WR / EC号指令的执行情况及其组成干预措施用作使用产前接触醇在人类的动物模型大鼠的更强大的治疗干预。我们也将讨论的程序元件是绝对必要的干预和哪些可以根据实验者的问题或设施来改变。

为了评估超级干预的效果，就要看它的每一个构成要素的影响 - WR和EC - 对我们感兴趣的措施。 图1至图 3（下文）出现在利用该范例8先前的出版物。 图4出现在博士论文36。这些数据说明WR-EC对海马成年神经齿状回的影响。所有的图表说明了组手段，具有指示从均值一个标准误差误差线...

Watch this Scientific Journal Video about Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD at JoVE.com

Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD

心血管锻炼，并在复杂的环境刺激的经历对啮齿动物大脑内的神经可塑性的多种措施积极效益。本文将讨论这些措施的实施作为"superintervention"相结合的车轮运转和环境的复杂性，将解决这些干预措施的限制。

车轮运行环境的复杂性在胎儿酒精中毒综合症的动物模型干预治疗

Aerobic exercise (e.g., wheel running (WR) extensively used in animal research) positively impacts many measures of neuroplastic potential in the brain, ...

wheel-running-environmental-complexity-as-therapeutic-intervention-an

Research

JoVE Journal

Behavior

6.7K 次观看.  University of Delaware. 心血管锻炼，并在复杂的环境刺激的经历对啮齿动物大脑内的神经可塑性的多种措施积极效益。本文将讨论这些措施的实施作为"superintervention"相结合的车轮运转和环境的复杂性，将解决这些干预措施的限制。 

视频: Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

一致性的任务作为一种手段来获取目标行为的措施中的橡胶手错觉范式Crossmodal

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

科研

行为学

Nest Building as an Indicator of Health and Welfare in Laboratory Mice

The minimization and alleviation of suffering has moral and scientific implications. In order to mitigate this negative experience one must be able to identify when an animal is actually in distress. Pain, illness, or distress cannot be managed if unrecognized. Evaluation of pain or illness typically involves the measurement of physiologic and behavioral indicators which are either invasive or not suitable for large scale assessment. The observation of nesting behavior shows promise as the basis of a species appropriate cage-side assessment tool for recognizing distress in mice. Here we demonstrate the utility of nest building behavior in laboratory mice as an ethologically relevant indicator of welfare. The methods presented can be successfully used to identify thermal stressors, aggressive cages, sickness, and pain. Observation of nest building behavior in mouse colonies provides a refinement to health and well-being assessment on a day to day basis.

We demonstrate the utility of nest building behavior in laboratory mice as an indicator of welfare. Nest scoring is a sensitive technique that is altered by temperature, illness, and aggression. The time to integrate into nest test (TINT) is a simple cage-side assessment that can detect postoperative pain.

The minimization and alleviation of  suffering has moral and scientific implications. In order to mitigate this  negative experience one must be able to ...

The Use of the Puzzle Box as a Means of Assessing the Efficacy of Environmental Enrichment

Environmental enrichment can dramatically influence the development and function of neural circuits. Further, enrichment has been shown to successfully delay the onset of symptoms in models of Huntington&#8217;s disease 1-4, suggesting environmental factors can evoke a neuroprotective effect against the progressive, cellular level damage observed in neurodegenerative disorders. The ways in which an animal can be environmentally enriched, however, can vary considerably. Further, there is no straightforward manner in which the effects of environmental enrichment can be assessed: most methods require either fairly complicated behavioral paradigms and/or postmortem anatomical/physiological analyses. This protocol describes the use of a simple and inexpensive behavioral assay, the Puzzle Box 5-7 as a robust means of determining the efficacy of increased social, sensory and motor stimulation on mice compared to cohorts raised in standard laboratory conditions. This simple problem solving task takes advantage of a rodent&#8217;s innate desire to avoid open enclosures by seeking shelter. Cognitive ability is assessed by adding increasingly complex impediments to the shelter&#8217;s entrance. The time a given subject takes to successfully remove the obstructions and enter the shelter serves as the primary metric for task performance. This method could provide a reliable means of rapidly assessing the efficacy of different enrichment protocols on cognitive function, thus paving the way for systematically determining the role specific environmental factors play in delaying the onset of neurodevelopmental and neurodegenerative disease.

Environmental enrichment provides a potential protective effect against neurodegenerative disorders. Currently, however, there is no easy way of determining the efficacy of enrichment procedures. This protocol describes a simple &#8220;Puzzle Box&#8221; method for assessing an animal&#8217;s cognitive function, in order to reveal the effectiveness of environmental enrichment.

该拼图方块的使用作为评价环境富集的功效的一种手段

Environmental enrichment can dramatically influence the development and function of neural circuits.  Further, enrichment has been shown to successfully ...

The Forced Swim Test as a Model of Depressive-like Behavior

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

在强迫游泳试验作为抑郁样行为的模型

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like ...

An Innovative Running Wheel-based Mechanism for Improved Rat Training Performance

This study presents an animal mobility system, equipped with a positioning running wheel (PRW), as a way to quantify the efficacy of an exercise activity for reducing the severity of the effects of the stroke&#160;in rats. This system provides more effective animal exercise training than commercially available systems such as treadmills and motorized running wheels (MRWs). In contrast to an MRW that can only achieve speeds below 20 m/min, rats are permitted to run at a stable speed of 30 m/min on a more spacious and high-density rubber running track supported by a 15 cm wide acrylic wheel with a diameter of 55 cm in this work. Using a predefined adaptive acceleration curve, the system not only reduces the operator error but also trains the rats to run persistently until a specified intensity is reached. As a way to evaluate the exercise effectiveness, real-time position of a rat is detected by four pairs of infrared sensors deployed on the running wheel. Once an adaptive acceleration curve is initiated using a microcontroller, the data obtained by the infrared sensors are automatically recorded and analyzed in a computer. For comparison purposes, 3 week training is conducted on rats using a treadmill, an MRW and a PRW. After surgically inducing middle cerebral artery occlusion (MCAo), modified neurological severity scores (mNSS) and an inclined plane test were conducted to assess the neurological damages to the rats. PRW is experimentally validated as the most effective among such animal mobility systems. Furthermore, an exercise effectiveness measure, based on rat position analysis, showed that there is a high negative correlation between the effective exercise and the infarct volume, and can be employed to quantify a rat training in any type of brain damage reduction&#160;experiments.

This study presents an innovative running wheel-based animal mobility system to quantify an effective exercise activity in rats. A rat-friendly testbed is built, using a predefined adaptive acceleration curve, and a high correlation between the effective exercise rate and the infarct volume suggests the protocol&#39;s potential for stroke prevention experiments.

为提高训练大鼠绩效的创新运行基于轮机制

This study presents an animal mobility system, equipped with a positioning running wheel (PRW), as a way to quantify the efficacy of an exercise activity ...

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 ...

Establishment of a Valuable Mimic of Alzheimer's Disease in Rat Animal Model by Intracerebroventricular Injection of Composited Amyloid Beta Protein

Alzheimer&#39;s disease (AD) is an irreversible, progressive brain disease that slowly destroys memory and is accompanied by neuron loss and structure change. With the increase of AD patients worldwide, the pathology and treatment of the disease has become a focus in the International Pharmaceutical Industry. Thus, the establishment of the animal model to mimic AD in the laboratory is of great importance.
Here, we describe a detailed protocol for establishing a mimic of AD in a rat animal model though intracerebroventricular injection of amyloid beta protein 25-35 (A&#946;25-35) combined with aluminum trichloride (AlCl3) and anterodorsal thalamic nucleus injection of recombinant human transforming growth factor-&#946;1 (RHTGF-&#946;1) to rats. The related markers of AD were measured, including: spatial memory, neuronal structure and substructure, neuronal A&#946;, and neurofibrillary tangles (NFT) production. This rat model demonstrates spatial memory impairment, neuronal structure and substructure pathological changes, neuron intracellular A&#946; burden, and NFT aggregation, and provides a close mimic of the neuronal structure and function disorder to that of clinical AD patients. Thus, the presented AD rat modelprovides a valuable in vivo tool for exploring neuronal function, neuronal pathology, and drug screening of AD.

This is a protocol to mimic Alzheimer&#39;s Disease in rats by evaluation of spatial memory impairment, neuronal pathological changes, neuronal amyloid beta protein (A&#946;) burden, and neurofibrillary tangles aggregation, induced by the injection of A&#946;25-35 combined with aluminum trichloride and recombinant human transforming growth factor-&#946;1.

脑室注射复合淀粉样蛋白β模型建立大鼠阿尔茨海默病的价值模拟

Alzheimer&#39;s disease (AD) is an irreversible, progressive brain disease that slowly destroys memory and is accompanied by neuron loss and structure ...

Testing Animal Anxiety in Rats: Effects of Open Arm Ledges and Closed Arm Wall Transparency in Elevated Plus Maze Test

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral science, conflicting outcomes are often provided from different laboratories. To identify reasons for the different outcomes, we previously focused on arm features, which differ between laboratories, most notably the presence/absence of ledges at the sides of open arms and the transparency/opaqueness of closed arm walls. In a previous report, we used a custom designed container to compare rat behavior on different combinations of open and closed arm designs under otherwise identical experimental conditions, and showed that differences in arm features interfere with experimental outcomes. In brief, open arm ledges significantly increased anxiety-like behavior in rats, while transparent arms may also have decreased this behavior. Furthermore, we verified a higher detection sensitivity of the effect of an anxiolytic drug in a combination of no-ledged open arm + opaque walled closed arm compared with a combination of ledged open arm + transparent walled closed arm. In this report, we introduce our protocol for the elevated plus maze test, together with discussion of the key results from the previous report and our experimental experience. We believe this report will provide useful information for researchers who have employed or who plan to use the elevated plus maze in their studies.

Rats' anxiety-like behavior tested by the elevated plus maze varies highly depending on the testing environment. Here we show how apparatus settings, especially arm structure, affect behavior on the maze, and we explain a reliable protocol to detect effects of anxiolytic drugs. This report will contribute to anxiety research.

大鼠动物焦虑症的实验研究: 开放臂壁和闭合臂墙透明度对高加迷宫试验的影响

The elevated plus maze test is a behavioral test for assessing animal anxiety in rodents. Although this test is widely applied in the field of behavioral ...

Nest Building Behavior as an Early Indicator of Behavioral Deficits in Mice

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare. In addition, nesting behavior is sensitive to many environmental and physiological challenges, as well as many genetic mutations underlying pathological disease states. The following protocol describes a nesting behavior paradigm that explores the usage of four types of nesting material. In addition, the protocol utilizes intraclass correlations to demonstrate that inter-rater reliability is higher when nests are constructed out of shredded paper compared to other common nesting materials such as cotton squares, paper twists, and soft cob bedding. The chosen methodology and statistical considerations (i.e., intraclass correlation) for this assay may be of interest for those conducting experiments assessing the quality of living of mice.&#160;

Here, we present a protocol to quantify nest building behavior in mice, which is known to be impaired in several neurological disorders and diseases. This protocol examines the utility of four materials and offers the opportunity to quantify the rater agreement in scoring, improving the validity and reliability of the assay.

巢穴建筑行为作为小鼠行为缺陷的早期指标

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents ...

The Use of Traditional Fear Tests to Evaluate Different Emotional Circuits in Cattle

Animal temperament is complex and has implications for productivity and economic profitability. Quantifying an animal&#39;s response to differing stimuli may facilitate breeding selections and identify animals that are better suited to specific management strategies. Multiple tests have been developed to evaluate cattle temperament (e.g., exit velocity, chute score, pen score, open field test, startle test, bovine zero maze), but each of these tests evaluates the animal&#39;s response to different stimuli (e.g., isolation, novel environment, startle, willingness to enter an enclosed area). Cattle temperament has been observed to be relatively stable over time. However, the evaluation of temperament has the potential to be influenced by current conditions, previous experiences, and observer bias. Many of these temperament tests have been improperly categorized as fear tests and have also been criticized for being subjective. This paper provides a framework for standardizing behavioral tests for cattle and suggests that these different evaluations assess different aspects of the animal&#39;s overall temperament.

Here, we present a protocol to conduct a variety of behavioral tests in cattle that have been designed to evaluate emotions. A battery of behavioral tests (open field test, startle test, bovine zero maze, exit velocity, pen score, and chute score) were conducted to evaluate different components of animal temperament.

使用传统恐惧测试来评估牛的不同情绪回路

Animal temperament is complex and has implications for productivity and economic profitability. Quantifying an animal&#39;s response to differing stimuli ...