威康信托基金会提供开放式访问英国牛津大学的资助。罗伯特执事牛津OXION组由威康信托基金赠款WT084655MA资助，是一个成员。

1。简介： 小鼠和大鼠，将最初只有少量使用一种新型食品。这被认为是因为它们一经定罪，中毒是由于他们无力呕吐。 唯一的例外是如果他们以前遇到的另一种动物吃的食物，如果他们闻到它从他们的同龄人呼出的空气，他们将划分为13安全。这是因为食物的气味与二硫化碳配对其他老鼠的呼吸 12 。事实上，二硫化碳本身增加小鼠和大鼠17的食品消费。这种现象被称为“社会输送食物的喜好”，可以作为一个简单的嗅觉学习范式22。这已经是敏感的海马3的病变， 但 5个其他研究未能复制这一发现。有人曾建议，新皮层的胆碱能神经系统，尤其是前额组件19日可能会超过为社会输送海马胆碱能系统的重要。社会输送甚至跟踪老年大鼠记忆障碍，可能是通过降低CREB的（内cAMP反应元件结合蛋白）在7岁海马传输介导的。 的啮齿类动物获得一个由社会输送的食物偏好的难易程度有强烈的影响hyponeophagia测试。当笔者是一个hyponeophagia测试与海马损毁和对照组大鼠，他意外地投入未来的对照组大鼠由于测试 8笼一个测试海马大鼠（吃了甜玉米） 。它吃了，在14章第只能控制，不会有延迟时间为300秒。因此，应十分注意采取措施防止此类食物气味的社会hyponeophagia测试期间传输。 如果第一次hyponeophagia测试不会导致在一个清晰，明确的结果，可以执行多个进一步的测试。图1-4说明了不同的仪器的例子。测试的情况下，可以制定的数量只受实验者的想象力。双向重复测量方差分析结果进行了分析。由于hyponophagia数据通常是非常变量，不符合高斯分布，往往倾斜一些很长的潜伏期的动物，它应该首先被转换，平方根或日志改造截断极端较长的潜伏期特别有用。 2。仪器： 图1-4给出hyponeophagia测试设置的例子。新型食品和环境的具体组合是不是很关键，但显然是最适合在图1所示的食物含有液体，也可以放置在它虽然甜玉米niblet。 在一般情况下，它是一个好主意，有大部分地板与食品所涉及的仪器。不仅动物出现厌恶找到这个不寻常的表面，这种技术还可以消除之前找到食物的困惑，由于勘探。因此，镇静药物可能会出现anxiogenic的，因为它增加了延迟和吃的食物，因为它郁闷的运动，不是因为它是anxiogenic。例如，一个出版表示将在一个开放的领域2中心食品。这一结果不仅在探索时间混淆喂养延迟，它也引入了一个额外的焦虑，即开放领域中部地区的反感方面，开阔介导的焦虑，这已涉及到避免捕食风险的一个经典测量自然栖息地的14。然而，在某些情况下，这实际上可能是一个实验所需的功能。 2中描述的实验的另一个缺点是，标准实验室议员诱饵，在开阔的中心。这双重的缺点，它不是小说，也不是非常可口的食物，如甜玉米或甜炼乳不同，。我们一直使用极端适口的饵料，不仅增加了是否吃或避免新食品的冲突，而且动物并不需要过多的食物被剥夺在测试之前，只有轻微的剥夺是必要的，所以这方面的这里介绍的协议体现了“求精”的方面的3R的罗素和Burch 20。 2.1程序： 投喂食物的老鼠在一夜之间。删除所有从笼中斗的食物测试前再给予1克/鼠标普通饮食，这是约三分之一，他们通常会吃什么日晚。如果他们组安置，确保件小，使所有的老鼠可以吃平分秋色。对其进行测试第二天早上，并尽快更换他们的食物，测试完成。 设置的选择hyponeophagia测试仪器，也是一种行之家笼的小鼠放在测试之前和期间，单独的小笼子。 （这样就避免了留在集团笼其余小鼠在焦虑增加，它可以发生，如果你逐步消除老鼠从一组，也是社会输送食物的喜好。它还在测试标准化助攻（组间和单独居住的动物） ，并确保动物是最佳的警觉。 将鼠标在测试仪器。测量延迟吃。这是定义不断吃/喝2-3号通常情况下，老鼠会嗅出或舔第一食品简要，但后来才开始连续吃无抑制。 也可采取其他措施。在设定期间所花费的时间进食，如喂奶后第一次开始2分钟，也可能在此期间消耗的食物量，也可以测量。脑部病变，有时会影响这些措施的差异 4 。 2.2如图1所示的装置运行一个hyponeophagia测试的具体细节： 一个半透明的塑料壶（近似体积的1.5升，15厘米直径的壶嘴凸出进一步2厘米）的测试仪器。使用全脂甜炼乳（雀巢品牌优秀）新食品与水的稀释50:50（以方便处理）。包含鼠标的基础上，促进牛奶的调查，上下颠倒放置的水罐与壶嘴形成了对食品的小壁龛。重点关注的鼠标以及牛奶，因此减少了治疗，可能会影响观感效果，或方向，食物来源。 鼠标放置面临远离井壶轻轻地放进位置，小心不要捕获鼠标的尾部。在仪器置于正常启动饮用水的延迟。牛奶吸不计;至少两个秒饮用水应该发生。计数任何粪便的玻璃，并注意任何排尿（但是请注意，这些措施将在仪器的影响）。截止时间是2分钟。如果鼠标没有醉，届时，从设备中删除，并测试另外一个或两个小鼠，然后重新测试一个失败的约3分钟后喝。这一次可能是焦虑水平的最佳选择，以减少，同时仍保留对设备状态的习惯。这个测试休息 - 再休息，复试的周期可以继续，直到鼠标吃或已经进行的试验设置。最多3项试验的结果在大多数饮用水过长而不做实验的老鼠。测试参数是喝的（累计）的延迟。 非实验小鼠气味其中可以发挥重要作用的其他测试，应放置在仪器测试开始之前。按照标准化清洁协议之间的所有小鼠。取出尿液/粪便，擦拭食物和干布/组织与潮湿的塑料基地。笔芯的食物有牛奶（约0.2​​毫升，轮辋井）。 <img src="/files/ftp_upload/2613/2613fig1.jpg" alt="图1"/> 图1。国内一个塑料壶hyponeophagia测试单元转换为使用。甜炼乳，可放置在位于内壶嘴的小食品，方便指示鼠标注意直。粘酒壶倒基地导致体重有助于稳定，反对任何对墙壁的运动鼠标。 <img src="/files/ftp_upload/2613/2613fig2.jpg" alt="图2"/> 图2包含两个白（焦虑发人深思）白色插入hyponeophagia测试观察室。甜玉米可作为新食品。 <img src="/files/ftp_upload/2613/2613fig3.jpg" alt="图3"/> 图3。另一个hyponeophagia测试单位。新颖的食品是猴子的治疗组合。 <img src="/files/ftp_upload/2613/2613fig4.jpg" alt="图4"/> 图4。另一个hyponeophagia测试单位。食品是混合切碎的坚果。 3。运行多个hyponophagia实验： 第一个hyponeophagia测试可能无法提供一个明确的结果。这种情况经常发生，并经常因基线（对照组）值过高或过低，造成天花板或地板效应。楼效果测试时遇到的海马损毁小鼠 10;似乎控制值要足够高，以观测Ë降低hyponeophagia。 它可以是难以判断测试情况的​​要求aversiveness。如果老鼠已经进行了几次测试已经（不一定要在焦虑相关的任务），他们的情绪化水平将低于，如果他们NA已经的行为测试，并须更anxiogenic测试。这往往可以提供一个测试环境中升高（如图4）。可以增加厌恶噪音测试的情况，如打一个响亮的卷或白噪声发生器在一个电台。更明亮的照明也将增加测试环境aversiveness。 因此，如果第一次的hyponeophagia结果并不重要，尝试几种不同的测试情况，并执行一个重复测量方差分析。这是一个非常强大的实验设计。 4。预期结果： 海马病变产生hyponeophagia在小鼠10强下降，近期未发表的作品，这是，因为在大鼠1，由于海马腹侧地区。缺乏KATP通道亚基Kir6.2的的小鼠显示增加了一个测试，但不hyponeophagia在另外 9，混乱的结果，但为重点，在测试环境中上的差异，可以有一个结果显着的效果，也点出有用执行多个测试。 129S2/SvHsd小鼠以上C57BL/6JolaHsd 6 hyponeophagic。事实上，几个近交系小鼠品系的比较表明标记应变间的差异 21 。

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hyponeophagia测试延迟的数字通常是高度可变的。这里描述的技术，对动物吃一个设定的时间，然后重新测试后，如果它不能吃，服务，以减少超长时间延迟的风险，并节省了实验者的时间。 优势hyponeophagia，焦虑测试，如加迷宫是，如果第一次测试的结果未能达到统计意义，其他测试运行使用不同的新的测试环境和食品的被测量焦虑的类型，似乎是相同的，由先前运行的测试，没有质的改变，不像在加迷宫16。然后，可以使用重复测量方差分析评估测试系列。 它是目前已知的情绪化的几个不同方面的总称“焦虑”11,15,18覆盖。小鼠显示hyponeophagia变化不一定会显示在开放领域的变化，高架十字迷宫或光暗箱测试。因此，对这些测试的脑神经系统的基本性能必须至少有所不同。例如，下丘脑和杏仁可能在hyponeophagia参加，因为他们（除其他事项外）调节食物摄入量有关。

hyponeophagia: a measure of anxiety in the mouse

今天之前，快速行动和烈性杀鼠剂，如α-氯醛尚未使用，害虫控制器的工作往往是阻碍这种现象被称为为“诱饵羞怯”。小鼠和大鼠不能呕吐，由于胃的心脏括约肌的松紧度，所以要克服潜在的食物毒性的问题，他们已经进化第一摄取只有非常小的新型物质的战略。摄入的金额，然后逐步增加，直到确定该物质是否安全和有营养的动物。因此，旧的老鼠捕手会先放一个适口性的物质，这是毒素的车辆出没的区域，如燕麦片。只有当大量被随便饮用，他们会再加入毒药，在不影响车辆的味道计算的金额。中毒诱饵，动物，现在很容易在大量进食，然后迅速执行其职能。 诱饵羞怯现在使用的行为实验室测量焦虑的一种方式。提供一个非常可口，但新颖的物质，如甜玉米，坚果或甜炼乳，以一种新颖的形势下的小鼠（或大鼠），如一个新的笼子。然后测量的延迟，消耗定义新的食物量。 罗伯特兆焦耳执事可以达到<a href="mailto:robert.deacon@psy.ox.ac.uk">robert.deacon @ psy.ox.ac.uk</a>

Watch this Scientific Journal Video about Hyponeophagia: A Measure of Anxiety in the Mouse at JoVE.com

Hyponeophagia: A Measure of Anxiety in the Mouse

小鼠和大鼠，由于其与生俱来的谨慎，最初是在消耗一种新型的食品，尤其是在一个新的地方缓慢。这hyponeophagia可以很容易地在实验室中测量，实验动物，即使是远低于其野生着急

Hyponeophagia：在小鼠的焦虑测量

Before the present day, when fast-acting and potent rodenticides such as alpha-chloralose were not yet in use, the work of pest controllers was often ...

hyponeophagia-a-measure-of-anxiety-in-the-mouse

Research

JoVE Journal

Neuroscience

21.8K 次观看.  University of Oxford. 小鼠和大鼠，由于其与生俱来的谨慎，最初是在消耗一种新型的食品，尤其是在一个新的地方缓慢。这hyponeophagia可以很容易地在实验室中测量，实验动物，即使是远低于其野生着急

视频: Hyponeophagia: A Measure of Anxiety in the Mouse

A Simple Way to Measure Ethanol Sensitivity in Flies

Low doses of ethanol cause flies to become hyperactive, while high doses are sedating. The sensitivity to ethanol-induced sedation of a given fly strain is correlated with that strain s ethanol preference, and therefore sedation is a highly relevant measure to study the genetics of alcohol responses and drinking. We demonstrate a simple way to expose flies to ethanol and measure its intoxicating effects. The assay we describe can determine acute sensitivity, as well as ethanol tolerance induced by repeat exposure. It does not require a technically involved setup, and can therefore be applied in any laboratory with basic fly culture tools.

A simple assay to measure the sedating effects of ethanol on Drosophila flies, based on the loss of righting reflex, is described.

一个简单的方法来衡量在果蝇的乙醇灵敏度

Low doses of ethanol cause flies to become hyperactive, while high doses are sedating. The sensitivity to ethanol-induced sedation of a given fly strain ...

科研

神经科学

Quantifying the Activity of cis-Regulatory Elements in the Mouse Retina by Explant Electroporation

Transcription factors within cellular gene networks control the spatiotemporal pattern and levels of expression of their target genes by binding to cis-regulatory elements (CREs), short (&tilde;300-600 bp) stretches of genomic DNA which can lie upstream, downstream, or within the introns of the genes they control. CREs (i.e., enhancers/promoters) typically consist of multiple clustered binding sites for both transcriptional activators and repressors1-3. They serve as logical integrators of transcriptional input giving a unitary output in the form of spatiotemporally precise and quantitatively exact promoter activity. Most studies of mammalian cis-regulation to date have relied on mouse transgenesis as a means of assaying the enhancer function of CREs4-5. This technique is time-consuming, costly and, on account of insertion site effects, largely non-quantitative. On the other hand, quantitative assays for mammalian CRE function have been developed in tissue culture systems (e.g., dual luciferase assays), but the in vivo relevance of these results is often uncertain. 
Electroporation offers an excellent alternative to traditional mouse transgenesis in that it permits both spatiotemporal and quantitative assessment of cis-regulatory activity in living mammalian tissue. This technique has been particularly useful in the analysis of cis-regulation in the central nervous system, especially in the cerebral cortex and the retina6-8. While mouse retinal electroporation, both in vivo and ex vivo, has been developed and extensively described by Matsuda and Cepko6-7,9, we have recently developed a simple approach to quantify the activity of photoreceptor-specific CREs in electroporated mouse retinas10. Given that the amount of DNA that is introduced into the retina by electroporation can vary from experiment to experiment, it is necessary to include a co-electroporated 'loading control' in all experiments. In this respect, the technique is very similar to the dual luciferase assay used to quantify promoter activity in cultured cells. 
When assaying photoreceptor cis-regulatory activity, electroporation is usually performed in newborn mice (postnatal day 0, P0) which is the time of peak rod production11-12. Once retinal cell types become post-mitotic, electroporation is much less efficient. Given the high rate of rod birth in newborn mice and the fact that rods constitute more than 70% of the cells in the adult mouse retina, the majority of cells that are electroporated at P0 are rods. For this reason, rod photoreceptors are the easiest retinal cell type to study via electroporation. The technique we describe here is primarily useful for quantifying the activity of photoreceptor CREs.

Quantifying the Activity of cis-Regulatory Elements in the Mouse Retina by Explant Electroporation

This protocol describes a simple and inexpensive way to quantify the activity of cis-regulatory elements (i.e., enhancer/promoters) in living mouse retinas via explant electroporation. DNA preparation, retinal dissection, electroporation, retinal explant culture, and post-fixation analysis and quantification are described.

量化的活动顺</em在小鼠视网膜>调控元件外植体电穿孔

Transcription factors within cellular gene networks control the spatiotemporal pattern and levels of expression of their target genes by binding to ...

A Dual Tracer PET-MRI Protocol for the Quantitative Measure of Regional Brain Energy Substrates Uptake in the Rat

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the rat. The developed method is a small-animal positron emission tomography (PET) protocol, in which&#160;11C-AcAc and 18F-fluorodeoxyglucose (18F-FDG) are injected sequentially in each animal. This dual tracer PET acquisition is possible because of the short half-life of 11C (20.4 min). The rats also undergo a magnetic resonance imaging (MRI) acquisition seven days before the PET protocol. Prior to image analysis, PET and MRI images are coregistered to allow the measurement of regional cerebral uptake (cortex, hippocampus, striatum, and cerebellum). A quantitative measure of 11C-AcAc and 18F-FDG brain uptake (cerebral metabolic rate; &#956;mol/100 g/min) is determined by kinetic modeling using the image-derived input function (IDIF) method. Our new dual tracer PET protocol is robust and flexible; the two tracers used can be replaced by different radiotracers to evaluate other processes in the brain. Moreover, our protocol is applicable to the study of brain fuel supply in multiple conditions such as normal aging and neurodegenerative pathologies such as Alzheimer&#39;s and Parkinson&#39;s diseases.

Small-animal positron emission tomography enables the assessment of the brain&#39;s two main energy substrates:&#160;glucose and ketones. In the present method, 11C-acetoacetate and 18F-fluorodeoxyglucose are injected sequentially in each animal, and their uptake is measured quantitatively in specific brain regions determined from the magnetic resonance images.

We present a method for comparing the uptake of the brain&#39;s two key energy substrates: glucose and ketones (acetoacetate [AcAc] in this case) in the ...

The Optokinetic Response as a Quantitative Measure of Visual Acuity in Zebrafish

Zebrafish are a proven model for vision research, however many of the earlier methods generally focused on larval fish or demonstrated a simple response. More recently adult visual behavior in zebrafish has become of interest, but methods to measure specific responses are new coming. To address this gap, we set out to develop a methodology to repeatedly and accurately utilize the optokinetic response (OKR) to measure visual acuity in adult zebrafish. Here we show that the adult zebrafish's visual acuity can be measured, including both binocular and monocular acuities. Because the fish is not harmed during the procedure, the visual acuity can be measured and compared over short or long periods of time. The visual acuity measurements described here can also be done quickly allowing for high throughput and for additional visual procedures if desired. This type of analysis is conducive to drug intervention studies or investigations of disease progression.

Zebrafish have been a valuable tool for many research areas. Here we demonstrate a method to elicit a visual response and calculate a functional visual acuity in the adult zebrafish.

在视动反应在斑马鱼视力的定量测量

Zebrafish are a proven model for vision research, however many of the  earlier methods generally focused on larval fish or demonstrated a simple  ...

A Simple Way to Measure Alterations in Reward-seeking Behavior Using Drosophila melanogaster

We describe a protocol for measuring ethanol self-administration in fruit flies (Drosophila melanogaster) as a proxy for changes in reward states. We demonstrate a simple way to tap into the fly reward system, modify experiences related to natural reward, and use voluntary ethanol consumption as a measure for changes in reward states. The approach serves as a relevant tool to study the neurons and genes that play a role in experience-mediated changes of internal state. The protocol is composed of two discrete parts: exposing the flies to rewarding and nonrewarding experiences, and assaying voluntary ethanol consumption as a measure of the motivation to obtain a drug reward. The two parts can be used independently to induce the modulation of experience as an initial step for further downstream assays or as an independent two-choice feeding assay, respectively. The protocol does not require a complicated setup and can therefore be applied in any laboratory with basic fly culture tools.

A Simple Way to Measure Alterations in Reward-seeking Behavior Using Drosophila melanogaster

We describe a protocol for inducing rewarding and nonrewarding experiences in fruit flies (Drosophila melanogaster) using voluntary ethanol consumption as a measure for changes in reward states.

一个简单的方法来衡量在改建悬赏寻求行为使用<em&gt;果蝇</em

We describe a protocol for measuring ethanol self-administration in fruit flies (Drosophila melanogaster) as a proxy for changes in reward states. We ...

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models

Neurotransmitter disruption is often a key component of diseases of the central nervous system (CNS), playing a role in the pathology underlying Alzheimer's disease, Parkinson's disease, depression, and anxiety. Traditionally, microdialysis has been the most common (lauded) technique to examine neurotransmitter changes that occur in these disorders. But because microdialysis has the ability to measure slow 1-20 minute changes across large areas of tissue, it has the disadvantage of invasiveness, potentially destroying intrinsic connections within the brain and a slow sampling capability. A relatively newer technique, the microelectrode array (MEA), has numerous advantages for measuring specific neurotransmitter changes within discrete brain regions as they occur, making for a spatially and temporally precise approach. In addition, using MEAs is minimally invasive, allowing for measurement of neurotransmitter alterations in vivo. In our laboratory, we have been specifically interested in changes in the neurotransmitter, glutamate, related to Alzheimer's disease pathology. As such, the method described here has been used to assess potential hippocampal disruptions in glutamate in a transgenic mouse model of Alzheimer's disease. Briefly, the method used involves coating a multi-site microelectrode with an enzyme very selective for the neurotransmitter of interest and using self-referencing sites to subtract out background noise and interferents. After plating and calibration, the MEA can be constructed with a micropipette and lowered into the brain region of interest using a stereotaxic device. Here, the method described involves anesthetizing rTg(TauP301L)4510 mice and using a stereotaxic device to precisely target sub-regions (DG, CA1, and CA3) of the hippocampus.

Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer&#039;s Mouse Models

Here, we describe the setup, software navigation, and data analysis for a spatially and temporally precise method of measuring tonic and phasic extracellular glutamate changes in vivo using enzyme-linked microelectrode arrays (MEA).

使用基于酶的生物传感器来衡量进补和阶段性谷氨酸在阿尔茨海默氏症小鼠模型

Neurotransmitter disruption is often a key component of diseases of the central nervous system (CNS), playing a role in the pathology underlying ...

Assay to Measure Nucleocytoplasmic Transport in Real Time within Motor Neuron-like NSC-34 Cells

Nucleocytoplasmic transport refers to the import and export of large molecules from the cell nucleus. Recently, a number of studies have shown a connection between amyotrophic lateral sclerosis (ALS) and impairments in the nucleocytoplasmic pathway. ALS is a neurodegenerative disease affecting the motor neurons and resulting in paralysis and ultimately in death, within 2-5 years on average. Most cases of ALS are sporadic, lacking any apparent genetic linkage, but 10% are inherited in a dominant manner. Recently, hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene were identified as a genetic cause of ALS and frontotemporal dementia (FTD). Importantly, different groups have recently proposed that these mutants affect nucleocytoplasmic transport. These studies have mostly shown the final outcome and manifestations caused by HREs on nucleocytoplasmic transport, but they do not demonstrate nuclear transport dysfunction in real time. As a result, only severe nucleocytoplasmic transport deficiency can be determined, mostly due to high overexpression or exogenous protein insertion. 
This protocol describes a new and very sensitive assay to evaluate and quantify nucleocytoplasmic transport dysfunction in real time. The rate of import of a NLS-NES-GFP protein (shuttle-GFP) can be quantified in real time using fluorescent microscopy. This is performed by using an exportin inhibitor, thus allowing the shuttle GFP only to enter the nucleus. To validate the assay, the C9orf72 HRE translated dipeptide repeats, poly(GR) and poly(PR), which have been previously shown to disrupt nucleocytoplasmic transport, were used. Using the described assay, a 50% decrease in the nuclear import rate was observed compared to the control. Using this system, minute changes in nucleocytoplasmic transport can be examined and the ability of different factors to rescue (even partially) a nucleocytoplasmic transport defect can be determined.

This protocol describes a method to sensitively measure the nucleocytoplasmic transport rate within motor neuron-like NSC-34 cells by quantifying the real-time change in the nuclear import of a NLS-NES-GFP protein.

测定在运动神经元样NSC-34细胞中实时测量核细胞质运输

Nucleocytoplasmic transport refers to the import and export of large molecules from the cell nucleus. Recently, a number of studies have shown a ...

The Power of Interstimulus Interval for the Assessment of Temporal Processing in Rodents

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in neurocognitive disorders. Despite the popularization of prepulse inhibition (PPI) in recent years, many current protocols promote using a percent of control measure, thereby precluding the assessment of temporal processing. The present study used cross-modal PPI and gap prepulse inhibition (gap-PPI) to demonstrate the benefits of employing a range of interstimulus intervals (ISIs) to delineate effects of sensory modality, psychostimulant exposure, and age. Assessment of sensory modality, psychostimulant exposure, and age reveals the utility of an approach varying the interstimulus interval (ISI) to establish the shape of the ISI function, including increases (sharper curve inflections) or decreases (flattening of the response amplitude curve) in startle amplitude. Additionally, shifts in peak response inhibition, suggestive of a differential sensitivity to the manipulation of ISI, are often revealed. Thus, the systematic manipulation of ISI affords a critical opportunity to evaluate temporal processing, which may reveal the underlying neural mechanisms involved in neurocognitive disorders.

Temporal processing, a preattentive process, may underlie deficits in higher-level cognitive processes, including attention, commonly observed in neurocognitive disorders. Using prepulse inhibition as an exemplar paradigm, we present a protocol for manipulating interstimulus interval (ISI) to establish the shape of the ISI function to provide an assessment of temporal processing.

间刺激间隔对啮齿类动物时间处理评估的力量

Temporal processing deficits have been implicated as a potential elemental dimension of higher-level cognitive processes, commonly observed in ...

Mechanical Conflict-Avoidance Assay to Measure Pain Behavior in Mice

Pain comprises of both sensory (nociceptive) and affective (unpleasant) dimensions. In preclinical models, pain has traditionally been assessed using reflexive tests that allow inferences regarding pain's nociceptive component but provide little information about the affective or motivational component of pain. Developing tests that capture these components of pain are therefore translationally important. Hence, researchers need to use non-reflexive behavioral assays to study pain perception at that level. Mechanical conflict-avoidance (MCA) is an established voluntary non-reflexive behavior assay, for studying motivational responses to a noxious mechanical stimulus in a 3 chamber paradigm. A change in a mouse's location preference, when faced with competing noxious stimuli, is used to infer the perceived unpleasantness of bright light versus tactile stimulation of the paws. This protocol outlines a modified version of the MCA assay which pain researchers can use to understand affective-motivational responses in a variety of mouse pain models. Though not specifically described here, our example MCA data use the intraplantar complete Freund's adjuvant (CFA), spared nerve injury (SNI), and a fracture/casting model as pain models to illustrate the MCA procedure.

The mechanical conflict-avoidance assay is used as a non-reflexive readout of pain sensitivity in mice which can be used to better understand affective-motivational responses in a variety of mouse pain models.

机械冲突避免测定测量小鼠疼痛行为

Pain comprises of both sensory (nociceptive) and affective (unpleasant) dimensions. In preclinical models, pain has traditionally been assessed using ...

Social Isolation Model: A Noninvasive Rodent Model of Stress and Anxiety

Anxiety disorders are one of the leading causes of disability in the United States (US). Current treatments are not always effective and less than 50% of patients achieve full remission. A critical step in developing a novel anxiolytic is to develop and utilize an animal model, such as mice, to study pathological changes and test drug target(s), efficacy, and safety. Current approaches include genetic manipulation, chronic administration of anxiety-inducing molecules, or the administration of environmental stress. These methods, however, may not realistically reflect anxiety induced throughout daily life. This protocol describes a novel anxiety model, which mimics the intentional or unintentional patterns of social isolation in modern life. The social isolation-induced anxiety model minimizes perceived distractions and invasiveness and utilizes wild type C57BL/6 mice. In this protocol, 6- to 8-week-old mice (male and female) are singly housed in opaque cages to visually block the external environment, such as neighboring mice, for 4 weeks. No environmental enrichments (such as toys) are provided, bedding material is reduced by 50%, any treatment of drug is administered as an agar form, and the exposure/handling of the mice is minimized. Socially isolated mice generated using this protocol exhibit greater anxiety-like behavior, aggression,&#160;as well as decreased cognition.

Presented here is a social isolation (SI)-induced anxiety mouse model that utilizes wild type C56BL/6J mice to induce stress and anxiety-like behavior with minimal handling and no invasive procedures. This model reflects modern life patterns of social isolation and is ideal for studying anxiety and related disorders.

社会隔离模型：压力和焦虑的非侵入性啮齿动物模型

Anxiety disorders are one of the leading causes of disability in the United States (US). Current treatments are not always effective and less than 50% of ...