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><tbody><tr><td>Female Time-pregnant Long Evans Rats</td><td>Envigo (Formerly: Harlan, Inc.)</td><td></td><td>Average litter size is 8 - 10 pups</td></tr><tr><td>Black India Ink</td><td>Higgins (Chartpak, Inc.)</td><td>44201</td><td></td></tr><tr><td>Syringes and Injection Needles</td><td>Becton, Dickinson and Company (BD)</td><td>Assorted</td><td>For injection of pawmarking ink, administration of milk-alcohol solution</td></tr><tr><td>Ear Punch</td><td>Kent Scientific Corporation</td><td>INS750076</td><td></td></tr><tr><td>Running Wheels</td><td>Wahmann Labs</td><td></td><td>Wahmann Running Wheel is discontinued. One per cage.</td></tr><tr><td>EC Cage</td><td>Martin&#039;s Cages, Inc.</td><td>R-695</td><td></td></tr><tr><td>Small EC Toys</td><td>Assorted</td><td></td><td></td></tr><tr><td>Medium EC Toys</td><td>Assorted</td><td></td><td>Should be able to fit 1 - 2 rats inside of/on top of object</td></tr><tr><td>Large EC Toys</td><td>Assorted</td><td></td><td>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

Universidad de Cartagena UDEC

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

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive &#8211; running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals&#8217; wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Here we present a protocol to induce activity-based anorexia (ABA) in female adolescent mice. ABA is a condition of hyperactivity evoked by imposing food restriction on rodents with access to a running wheel. This phenomenon is being used as a model to study the underlying neurobiology of anorexia nervosa.

使用基于活动的厌食症啮齿动物模型来研究神经性厌食症的神经生物学基础

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A ...

科研

行为学

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 ...

Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and validated for rat use. The Radial Water Tread (RWT) maze test of spatial memory (designed specifically for mice and requiring no swimming) has been shown previously to successfully distinguish between controlled cortical impact-induced TBI mice and sham controls. Here, a detailed protocol for this task is presented. The RWT maze capitalizes on the natural tendency of mice to avoid open areas in favor of hugging the sides of an apparatus (thigmotaxis). The walls of the maze are lined with nine escape holes placed above the floor of the apparatus, and mice are trained to use visual cues to locate the escape hole that leads out of the maze. The maze is filled with an inch of cold water, sufficient to motivate escape but not deep enough to require that the mouse swim. The acquisition period takes only four training days, with a test of memory retention on day five and a long-term memory test on day 12. The results reported here suggest that the RWT maze is a feasible alternative to rat-validated, swimming-based cognitive tests in the assessment of spatial memory deficits in mouse models of TBI.

Here we present a protocol for a mouse-specific test of cognition that does not require swimming. This test can be used to successfully distinguish controlled cortical impact-induced traumatic brain injury mice from sham controls.

使用径向水痕迷宫评估外伤性脑损伤小鼠模型中的空间记忆障碍

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and ...

Assessing Activity-based Anorexia in Mice

Rodents develop activity-based anorexia (ABA) when exposed to a restricted feeding schedule and allowed free access to a running wheel. These conditions lead to a life-threatening reduction in body weight. However, rodents exposed to only one of these conditions ultimately adapt to re-establish normal body weight. Although increased running coupled with reduction in voluntary food intake appear paradoxical under ABA conditions, ABA behavior is observed across numerous mammalian species. 
The ABA paradigm provides an animal model for anorexia nervosa (AN), an eating disorder with severe dysregulation of appetite-behavior. Subjects are singly housed with free access to a running wheel. Each day, the subject is offered food for a limited amount of time. During the course of the experiment, a subject's body weight decreases from high activity and low caloric intake. The duration of the study varies based on how long food is offered daily, the type of food offered, the strain of mouse, if drugs are being tested, and environmental factors.
A lack of effective pharmacological treatments for AN patients, their low quality of life, high cost of treatment, and their high mortality rate indicate the urgency to further research AN. We provide a basic outline for performing ABA experiments with mice, offering a method to investigate AN-like behavior in order to develop novel therapies. This protocol is optimized for use in Balb/cJ mice, but can easily be manipulated for other strains, providing great flexibility in working with different questions, especially related to genetic factors of ABA.

Mice individually housed with a running wheel while given limited access to food develop reductions in food consumption and increase activity on the running wheel. This experimental phenomenon is called activity-based anorexia. This paradigm provides an experimental tool for studying the neurobiology and behaviors underlying aspects of anorexia nervosa.

小鼠活动性厌食症的评估

Rodents develop activity-based anorexia (ABA) when exposed to a restricted feeding schedule and allowed free access to a running wheel. These conditions ...

Tracking Individual Running Metrics in Mice Using a Voluntary Wheel Running Protocol that Minimizes Social Isolation

Voluntary wheel running (VWR) in rodents is used to evaluate performance and endurance and to simulate exercise. In contrast to other exercise paradigms that require aversive stimulus to induce active movement, wheel running is voluntary. VWR generally consists of placing a running wheel inside the mouse home cage. However, analyzing exercise parameters can typically only be conducted when mice are individually housed, while overall cage effects can be reported when mice are group-housed. Therefore, the current models force experimenters to choose between measuring individual exercise parameters in single-housed mice or measuring group effects in group-housed mice; depending on the research question and model, this could be limiting. 
Therefore, the goal of this method is to demonstrate a protocol that assesses VWR in a mouse model by quantifying running parameters in individual mice, with minimal isolation. We report on device design, preoperative preparations, and experiment setup. Results of a 6-week training protocol using this VWR model suggest it provides sufficient stimulus to increase spatial object recognition memory, comparable to the clinical effect of exercise. This simple and inexpensive model facilitates investigation into the effect of VWR on multiple measurements of wheel activity, minimizing factors that could limit or affect experimental outcomes.

This protocol describes an effective voluntary wheel-running model that can be implemented in various research contexts. Unlike other voluntary running models, this method avoids isolation housing while tracking running metrics in individual mice.

Voluntary wheel running (VWR) in rodents is used to evaluate performance and endurance and to simulate exercise. In contrast to other exercise paradigms ...

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke.
For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.

To investigate the co-morbid Alzheimer&#39;s disease (AD) and stroke condition in a novel model, three behavior tasks are described that assess both motor control and cognitive behaviors. These tasks include the beam-walk task, cylinder task and Morris water maze.

汽车和海马依赖空间学习和记忆参考评估与中风阿尔茨海默氏病的转基因大鼠模型

Alzheimer&#39;s disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk ...

医学

Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats

Spinal cord injury (SCI) results in lasting deficits that include both mobility and a multitude of autonomic-related dysfunctions. Locomotor training (LT) on a treadmill is widely used as a rehabilitation tool in the SCI population with many benefits and improvements to daily life. We utilize this method of activity-based task-specific training (ABT) in rodents after SCI to both elucidate the mechanisms behind such improvements and to enhance and improve upon existing clinical rehabilitation protocols. Our current goal is to determine the mechanisms underlying ABT-induced improvements in urinary, bowel, and sexual function in SCI rats after a moderate to severe level of contusion. After securing each individual animal in a custom-made adjustable vest, they are secured to a versatile body weight support mechanism, lowered to a modified three-lane treadmill and assisted in step-training for 58 minutes, once a day for 10 weeks. This setup allows for the training of both quadrupedal and forelimb-only animals, alongside two different non-trained groups. Quadrupedal-trained animals with body weight support are aided by a technician present to assist in stepping with proper hind limb placement as necessary, while forelimb-only trained animals are raised at the caudal end to ensure no hind limb contact with the treadmill and no weight-bearing. One non-trained SCI group of animals is placed in a harness and rests next to the treadmill, while the other control SCI group remains in its home cage in the training room nearby. This paradigm allows for the training of multiple SCI animals at once, thus making it more time-efficient in addition to ensuring that our pre-clinical animal model mimics the clinical representation as close as possible, particularly with respect to the body weight support with manual assistance.

This protocol demonstrates our model of activity-based locomotor treadmill training for rats with spinal cord injury (SCI). Included is both quadrupedal and forelimb-only groups, in addition to two distinct types of non-trained control groups. Investigators are able to assess training effects on SCI rats using this protocol.

脊髓损伤 wistar 大鼠跑步机的作业训练

Spinal cord injury (SCI) results in lasting deficits that include both mobility and a multitude of autonomic-related dysfunctions. Locomotor training (LT) ...

神经科学

WheelCon: A Wheel Control-Based Gaming Platform for Studying Human Sensorimotor Control

Feedback control theory has been extensively implemented to theoretically model human sensorimotor control. However, experimental platforms capable of manipulating important components of multiple feedback loops lack development. This paper describes WheelCon, an open-source platform aimed at resolving such insufficiencies. Using only a computer, a standard display, and inexpensive gaming steering wheel equipped with a force feedback motor, WheelCon safely simulates the canonical sensorimotor task of riding a mountain bike down a steep, twisting, bumpy trail. The platform provides flexibility, as will be demonstrated in the demos provided, so that researchers may manipulate the disturbances, delay, and quantization (data rate) in the layered feedback loops, including a high-level advanced plan layer and a low-level delayed reflex layer. In this paper, we illustrate WheelCon&#39;s graphical user interface (GUI), the input and output of existing demos, and how to design new games. In addition, we present the basic feedback model and the experimental results from the demo games, which align well with the model&#39;s prediction. The WheelCon platform can be downloaded at https://github.com/Doyle-Lab/WheelCon. In short, the platform is featured to be cheap, simple to use, and flexible to program for effective sensorimotor neuroscience research and control engineering education.

WheelCon is a novel, free and open-source platform to design video games that noninvasively simulates mountain biking down a steep, twisting, bumpy trail. It contains components presenting in human sensorimotor control (delay, quantization, noise, disturbance, and multiple feedback loops) and allows researchers to study the layered architecture in sensorimotor control.

轮式康:一个基于车轮控制的游戏平台，用于研究人类传感器运动控制

Feedback control theory has been extensively implemented to theoretically model human sensorimotor control. However, experimental platforms capable of ...

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

Functional ultrasound (fUS) imaging is a novel brain imaging modality that relies on the high-sensitivity measure of the cerebral blood volume achieved by ultrafast doppler angiography. As brain perfusion is strongly linked to local neuronal activity, this technique allows the whole-brain 3D mapping of task-induced regional activation as well as resting-state functional connectivity, non-invasively, with unmatched spatio-temporal resolution and operational simplicity. In comparison with fMRI (functional magnetic resonance imaging), a main advantage of fUS imaging consists in enabling a complete compatibility with awake and behaving animal experiments. Moreover, fMRI brain mapping in mice, the most used preclinical model in Neuroscience, remains technically challenging due to the small size of the brain and the difficulty to maintain stable physiological conditions. Here we present a simple, reliable and robust protocol for whole-brain fUS imaging in anesthetized and awake mice using an off-the-shelf commercial fUS system with a motorized linear transducer, yielding significant cortical activation following sensory stimulation as well as reproducible 3D functional connectivity pattern for network identification.

This protocol describes the quantification of volumetric cerebral hemodynamic variations in the mouse brain using functional ultrasound (fUS). Procedures for 3D functional activation map following sensory stimulation as well as resting-state functional connectivity are provided as illustrative examples, in anesthetized and awake mice.

使用经颅功能超声成像的小鼠全脑3D激活和功能连接映射

Functional ultrasound (fUS) imaging is a novel brain imaging modality that relies on the high-sensitivity measure of the cerebral blood volume achieved by ...

Multifactorial Assessment of Motor Behavior in Rats after Unilateral Sciatic Nerve Crush Injury

The induction of a peripheral nerve injury is a widely used method in neuroscience for the assessment of repair and pain mechanisms among others. In addition, in the research field of movement disorders, sciatic crush injury has been employed to trigger a dystonia-like phenotype in genetically predisposed DYT-TOR1A rodent models of dystonia. To achieve consistent, reproducible and comparable results after a sciatic nerve crush injury, a standardized method for inducing the nerve crush is essential, in addition to a standardized phenotypical characterization. Attention must be paid not only to the specific assortment of behavioral tests, but also to the technical requirements, the correct execution and consecutive data analysis. This protocol describes in detail how to perform a sciatic nerve crush injury and provides a behavioral test battery for the assessment of motor deficits in rats that includes the open field test, the CatWalk XT gait analysis, the beam walking task, and the ladder rung walking task.

We provide a protocol for the assessment of motor behavior via a behavioral test battery in rats after sciatic nerve crush injury.

单边坐骨神经粉碎损伤后大鼠运动行为的多因素评估

The induction of a peripheral nerve injury is a widely used method in neuroscience for the assessment of repair and pain mechanisms among others. In ...