XHTW WM凯克基金会杰出青年学者在医学研究中，也是由美国国立卫生研究院/ NHLBI补助R01 - HL089598和R01HL091947和肌肉萎缩症协会授予＃69238的支持。这项工作是支持部分由基金会Leducq CaMKII信号在心脏联盟。 NL是2009-2010年的米歇尔Mirowski国际奖学金在接受心脏起搏与电从心脏节律协会和2009-2012年美国心脏协会博士后奖学金。

第1部分。手术准备<ol><li>编程的电刺激实验是在小鼠的生存期手术无菌条件下是必要的。然而，在本质上是最常见的类型的实验终端，普通明确的手术技巧不够的。 </li><li>鼠标使用2％，在0.5 L / min的100％O 2的异氟醚麻醉。 </li><li>卷发器是用来刮胡子的皮草，从领口到中期胸部水平。 </li><li>麻醉鼠标被放置在一个仰卧的姿势，其四肢录音心电图电极在加热板（梧桐仪器，休斯敦，得克萨斯州）成立上。手术区消毒，用10％聚维酮碘。建议的系统，包括直肠温度探头连接到一个加热垫，由一个thermoanalyzer系统控制，体温保持在37.0 ° C ± 1.0 ° C。 </li></ol>第2部分。插管和EP的导管插入右心房和心室<ol><li>脚趾捏鼠标完全麻醉，确认后，1 / 2英寸的切口中线右侧骶管总站与锁骨水平。 </li><li>分隔钝性分离皮下组织，唾液腺和淋巴组织，以可视化的右颈内静脉。 </li><li>与近端的静脉用6-0缝合。轻轻地拉动这个缝合，将保持直颈内静脉插入导管。另一个缝合静脉划归在可视化段的末端。这缝线将导管绑在一次心导管放置在最佳状态，以确保止血和保持在所需的位置（ 图1）导管。 </li><li>基于计算机的数据采集，现在开始记录体表心电图同时腔内电图（即IOX - 2数据采集软件，Emka技术，弗吉尼亚州，美国）和4个信息。心腔内电图记录，导管上的电极连接在“录音”模式（即STG3008模型，多通道系统，罗伊特林根，德国）的外部刺激。 </li><li>使用微型剪刀，在纵向方向的静脉，是一个小切口和先进1.1F octapolar导管（EPR - 800，米勒仪器，休斯顿，德克萨斯）是通过静脉流入右心房。轻轻拉动近端缝合，将有助于保持直颈内静脉，将允许更容易通过导管进入右心房和心室。验证正确的导管位置是由4腔内电图的波形图的可视化右心室，右心室，房室结，右心房的基地，分别为（图2）的顶点水平。 </li><li>现在与远端缝合关闭，以确保导管的位置，并防止可能发生的的出血。 </li></ol>第3部分。程控刺激<ol><li>在选择性心房调搏的情况下，位于中庭内的电极对“重新编码”模式切换“刺激”的模式，而另一个电极对留在“录音”模式。 </li><li>要确定鼠标是否有房性心律失常的脆弱性增加，右心房的电刺激进行编程。首先，心房起搏阈值确定的应用，在不同的基本周期长度（BCL）中的2毫秒（至少50个）的电流脉冲刺激捕获的一致性测试。初始脉冲列车BCL略高于内在BCL较低，是10毫秒（例如，100毫秒，90毫秒，80毫秒，70毫秒）下降。典型的电流刺激捕获所需的幅度是100-200μA。 </li><li>窦房结恢复时间（SNRT）测量后，申请在100毫秒BCL一个15秒的心房起搏列车。 SNRT最后的刺激和起搏列车第一次自发的窦性搏动的发生之间的时间间隔定义为。 </li><li>心房有效不应期（AERP）是由心房起搏列车系列应用在一个固定的BCLS一个加上较短的S2过早刺激（即100毫秒）。 S1 - S2的时间间隔逐步减少2 - MS在每个起搏列车从70ms的20ms的。 AERP定义为最长的S1 - S2的心房耦合故障间隔生成一个定期列车脉冲S2（S1和S2过早刺激）传播击败。彼此之间的刺激协议，是一个至少30秒的恢复期。 </li><li>房室的有效不应期（AV）是由节点（AVNERP）申请在100毫秒BCL耦合S2过早刺激心房起搏列车系列。 S1 - S2的时间间隔是逐步减少2 MS每个起搏列车从70毫秒到20毫秒。 AVNERP被定义为S1 - S2的耦合最长的间隔过早刺激传递到心房是由他的潜力，而不是由QRS波群。彼此之间的刺激协议，是一个至少30秒的恢复期。 </li><li>诱发房性心律失常，包括心房纤维颤动（AF），可使用Verheule 等突发起搏协议测试2 2秒阵阵应用于确定房性心律失常的诱发。第2次爆裂，一个40毫秒的周期长度（CL），和一个2 - MS CL比以前爆裂短，每次连续2秒爆裂，直到最终CL 20毫秒。在心律失常基板的情况下，心脏会立即恢复窦性心律，起搏协议。在心房扑动的情况下，将会有一个快速一个心房电图上看到的波规律，而心室反应的频率通常是慢，心室电图上看到。房颤的情况下，体表心电图P波的情况下将显示在不规则的RR间隔。此外，心房电图，就会发现一个快速和不规则波，而心室电图将揭示不规则和较慢的心室波（ 图3） 。通常心律失常感应协议一式三份，被认为是存在的，如果它可以在至少有2 3项试验诱发心律失常 。 3,4。 </li></ol>第4部分。拔除尿管<ol><li>所有起搏协议完成后，数据采集停止。在导管的末端缝合轻轻切断，以释放导管。 </li><li>在终端EP研究的情况下，结轻轻地松开释放导管。 </li><li>在研究的结论，将鼠标人道安乐死，而下异氟醚使用颈椎脱位。 </li></ol>代表性的成果体表心电图和心内电图记录同时在整个体内的电生理学研究，并完成所有协议的详细审查。基准电参数包括PQ的时间间隔，PR间期，QRS时限，QT间期，QRS形态。可以测量这些参数，手动或自动使用数据采集软件IOX - 2或心电图自动（Emka技术，弗吉尼亚州，美国）。 SNRT，AERP和AVNERP提供有关窦房结“领跑者”的功能，心房，房室结传导性能，分别的信息。起搏诱发房颤发作的例子，可以发现在纸， 车路等。 <img src="/files/ftp_upload/1730/1730fig1.jpg" alt="图1" /> 图1。腔内导尿在小鼠体内的电生理学研究的插图。右侧颈内静脉是孤立的，空心的。静脉末端打结一次取得适当的导管位置，B 。鼠标被放置在此过程中仰卧位C.卡通描绘的导管腔内的位置。对电极定位于右心室，右心室的基础，房室结，右心房的顶点水平， 分别为， D。特写1.1F octapolar导管。图Mathur 等人的修改。中国保监会Arrhtyhm Electrophys 5的许可。 <img src="/files/ftp_upload/1730/1730fig2.jpg" alt="图2" /> 图2。在鼠标的代表体表心电图和心内电图 。 （一）体表心电图显示正常窦性节律，频率为540次每分钟。（BE）的双极心内电图的录音（二）在右心房水平，房室结（三），和基地铅II配置（四）右心室，右心室（E）的顶点分别。请注意，在B组的A波腔内对应体表心电图的P波。心室电图的V型波对应体表心电图上QRS波。 <img src="/files/ftp_upload/1730/1730fig3.jpg" alt="图3" /> 图3。在鼠标后心房突发起搏房颤代表体表心电图和心内电图。

<ol>
	<li>Nattel, S., Shiroshita-Takeshita, A., Brundel, B. J., Rivard, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+of+atrial+fibrillation:+lessons+from+animal+models.">Mechanisms of atrial fibrillation: lessons from animal models.</a> Prog Cardiovasc Dis. 48, 9-9 (2005).</li><li>Verheule, S., Sato, T., Everett, T. t., Engle, S. K., Otten, D., Rubart-von der Lohe, M., Nakajima, H. O., Nakajima, H., Field, L. J., Olgin, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+vulnerability+to+atrial+fibrillation+in+transgenic+mice+with+selective+atrial+fibrosis+caused+by+overexpression+of+TGF-beta1.">Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1.</a> Circ Res. 94, 1458-1458 (2004).</li><li>Sood, S., Chelu, M. G., Oort, R. J. v. a. n., Skapura, D., Santonastasi, M., Dobrev, D., Wehrens, X. H., H, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracellular+calcium+leak+due+to+FKBP12.6+deficiency+in+mice+facilitates+the+inducibility+of+atrial+fibrillation.">Intracellular calcium leak due to FKBP12.6 deficiency in mice facilitates the inducibility of atrial fibrillation.</a> Heart Rhythm. 5, 1047-1047 (2008).</li><li>Chelu, M. G., Sarma, S., Sood, S., Wang, S., van Oort, R. J., Skapura, D. G., Li, N., Santonastasi, M., Muller, F. U., Schmitz, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Calmodulin+kinase+II-mediated+sarcoplasmic+reticulum+Ca2++leak+promotes+atrial+fibrillation+in+mice.">Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice.</a> J Clin Invest. 119, 1940-1940 (2009).</li><li>Mathur, N., Subeena, S., Wang, S., van Oort, R. J., Sarma, S., Li, N., Skapura, D., Bayle, J. H., Valderrabano, M., Wehrens, X. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sudden+Infant+Death+Syndrome+in+Mice+With+an+Inherited+Mutation+in+RyR.">Sudden Infant Death Syndrome in Mice With an Inherited Mutation in RyR.</a> Circ Arrhythmia Electrophysiol. , (2009).</li></ol>

在心脏导管插入术，导尿过程中的广泛出血，可能会增加心率由于血容量不足。在这种情况下，腹腔注射无菌生理盐水（0.3 1.0毫升）可以正常化充盈压，减少鼠标的血流动力学压力。 吸入异氟醚的时间超过2小时，或异氟醚的浓度较高（&gt; 2％），能抑制在小鼠的心脏和呼吸功能。因此，建议所有的研究，在不到2个小时完成。此外，它是必不可少的，体​​温始终维持在正?...

programmed electrical stimulation in mice

转基因小鼠已成为一个较好的动物模型，研究底层的传导异常，心房和心室心律不齐，心脏猝死的分子机制。<sup&gt; 1</sup&gt;心内起搏研究可以进行小鼠使用1.1​​F octapolar的导管插入颈静脉，流入右心房和心室先进。在这里，我们说明了在执行编程小鼠电刺激所涉及的步骤。体表心电图和心内电图同步记录在心房，房室交界区，心肌，而心内起搏的心房使用一个外部的刺激。因此，程控电刺激的小鼠提供了独特的机会，发掘潜在的传导缺陷和心律失常的分子机制。

Watch this Scientific Journal Video about Programmed Electrical Stimulation in Mice at JoVE.com

Programmed Electrical Stimulation in Mice

程控电刺激的能力，以确定心脏的传导性能，并有可能诱发和终止使用各种起搏协议心律不齐。使用经静脉导管，心内电图的录音，可以得到以下编程的电刺激协议，以确定心律失常基板的小鼠。

程控电刺激小鼠

Genetically-modified mice have emerged as a preferable animal model to study the molecular mechanisms underlying conduction abnormalities, atrial and ...

programmed-electrical-stimulation-in-mice

Research

JoVE Journal

Medicine

20.3K 次观看.  Baylor College of Medicine (BCM). 程控电刺激的能力，以确定心脏的传导性能，并有可能诱发和终止使用各种起搏协议心律不齐。使用经静脉导管，心内电图的录音，可以得到以下编程的电刺激协议，以确定心律失常基板的小鼠。

视频: Programmed Electrical Stimulation in Mice

Long-term Potentiation of Perforant Pathway-dentate Gyrus Synapse in Freely Behaving Mice

Studies of long-term potentiation of synaptic efficacy, an activity-dependent synaptic phenomenon having properties that make it attractive as a potential cellular mechanism underlying learning and information storage, have long been used to elucidate the physiology of various neuronal circuits in the hippocampus, amygdala, and other limbic and cortical structures. With this in mind, transgenic mouse models of neurological diseases represent useful platforms to conduct long-term&#160;potentiation (LTP) studies to develop a greater understanding of the role of genes in normal and abnormal synaptic communication in neuronal networks involved in learning, emotion and information processing. This article describes methodologies for reliably inducing LTP in the freely behaving mouse. These methodologies can be used in studies of transgenic and knockout freely&#160;behaving mouse models of neurodegenerative diseases.

Transgenic and knockout mouse models of neurological diseases are useful for studying the role of genes in normal and abnormal neurophysiology. This article describes methodologies which can be used to study long-term potentiation, a cellular mechanism which may underlie learning and memory, in transgenic and knockout freely&#160;behaving mouse models of neuropathology.

穿通通路 - 齿状回突触在自由活动的小鼠长时程增强

Studies of long-term potentiation of synaptic efficacy, an activity-dependent synaptic phenomenon having properties that make it attractive as a potential ...

科研

行为学

A Murine Model of Muscle Training by Neuromuscular Electrical Stimulation

Neuromuscular electrical stimulation (NMES) is a common clinical modality that is widely used to restore1, maintain2 or enhance3-5 muscle functional capacity. Transcutaneous surface stimulation of skeletal muscle involves a current flow between a cathode and an anode, thereby inducing excitement of the motor unit and the surrounding muscle fibers. 
NMES is an attractive modality to evaluate skeletal muscle adaptive responses for several reasons. First, it provides a reproducible experimental model in which physiological adaptations, such as myofiber hypertophy and muscle strengthening6, angiogenesis7-9, growth factor secretion9-11, and muscle precursor cell activation12 are well documented. Such physiological responses may be carefully titrated using different parameters of stimulation (for Cochrane review, see 13). In addition, NMES recruits motor units non-selectively, and in a spatially fixed and temporally synchronous manner14, offering the advantage of exerting a treatment effect on all fibers, regardless of fiber type. Although there are specified contraindications to NMES in clinical populations, including peripheral venous disorders or malignancy, for example, NMES is safe and feasible, even for those who are ill and/or bedridden and for populations in which rigorous exercise may be challenging. 
Here, we demonstrate the protocol for adapting commercially available electrodes and performing a NMES protocol using a murine model. This animal model has the advantage of utilizing a clinically available device and providing instant feedback regarding positioning of the electrode to elicit the desired muscle contractile effect. For the purpose of this manuscript, we will describe the protocol for muscle stimulation of the anterior compartment muscles of a mouse hindlimb.

A murine model of neuromuscular electrical stimulation (NMES), a safe and inexpensive clinical modality, to the anterior compartment muscles is described. This model has the advantage of modifying a readily available clinical device for the purpose of eliciting targeted and specific muscle contractions in mice.

一个小鼠模型，通过神经肌肉电刺激肌肉训练

Neuromuscular electrical stimulation (NMES) is a common clinical modality that is widely used to restore1, maintain2 or enhance3-5 muscle functional ...

医学

Two Different Real-Time Place Preference Paradigms Using Optogenetics within the Ventral Tegmental Area of the Mouse

Understanding how neuronal activation leads to specific behavioral output is fundamental for modern neuroscience. Combining optogenetics in rodents with behavioral testing in validated paradigms allows the measurement of behavioral consequences upon stimulation of distinct neurons in real-time with high spatial and temporal selectivity, and thus the establishment of causal relationships between neuronal activation and behavior. Here, we describe a step-by-step protocol for a real-time place preference (RT-PP) paradigm, a modified version of the classical conditioned place preference (CPP) test. The RT-PP is performed in a three-compartment apparatus and can be utilized to answer if optogenetic stimulation of a specific neuronal population is rewarding or aversive. We also describe an alternative version of the RT-PP protocol, the so-called neutral compartment preference (NCP) protocol, which can be used to confirm aversion. The two approaches are based on extensions of classical methodology originating from behavioral pharmacology and recent implementation of optogenetics within the neuroscience field. Apart from measuring place preference in real time, these setups can also give information regarding conditioned behavior. We provide easy-to-follow step-by-step protocols alongside examples of our own data and discuss important aspects to consider when applying these types of experiments.

Here we present two easy-to-follow step-by-step protocols for place preference paradigms using optogenetics in mice. Using these two different setups, preference and avoidance behaviors can be solidly assessed within the same apparatus with high spatial and temporal selectivity, and in a straightforward manner.

在小鼠的文室内使用光遗传学的两种不同的实时位置偏好范式

Understanding how neuronal activation leads to specific behavioral output is fundamental for modern neuroscience. Combining optogenetics in rodents with ...

Optogenetic Manipulation of Neuronal Activity to Modulate Behavior in Freely Moving Mice

Optogenetic modulation of neuronal circuits in freely moving mice affects acute and long-term behavior. This method is able to perform manipulations of single neurons and region-specific transmitter release, up to whole neuronal circuitries in the central nervous system, and allows the direct measurement of behavioral outcomes. Neurons express optogenetic tools via an injection of viral vectors carrying the DNA of choice, such as Channelrhodopsin2 (ChR2). Light is brought into specific brain regions via chronic optical implants that terminate directly above the target region. After two weeks of recovery and proper tool-expression, mice can be repeatedly used for behavioral tests with optogenetic stimulation of the neurons of interest.
Optogenetic modulation has a high temporal and spatial resolution that can be accomplished with high cell specificity, compared to the commonly used methods such as chemical or electrical stimulation. The light does not harm neuronal tissue and can therefore be used for long-term experiments as well as for multiple behavioral experiments in one mouse. The possibilities of optogenetic tools are nearly unlimited and enable the activation or silencing of whole neurons, or even the manipulation of a specific receptor type by light.
The results of such behavioral experiments with integrated optogenetic stimulation directly visualizes changes in behavior caused by the manipulation. The behavior of the same animal without light stimulation as a baseline is a good control for induced changes. This allows a detailed overview of neuronal types or neurotransmitter systems involved in specific behaviors, such as anxiety. The plasticity of neuronal networks can also be investigated in great detail through long-term stimulation or behavioral observations after optical stimulation. Optogenetics will help to enlighten neuronal signaling in several kinds of neurological diseases.

With optogenetic manipulation of specific neuronal populations or brain regions, behavior can be modified with high temporal and spatial resolution in freely moving animals. By using different optogenetic tools in combination with chronically implanted optical fibers, a variety of neuronal modulations and behavioral testing can be performed.

神经活性的光遗传学操作，调节自由移动小鼠的行为

Optogenetic modulation of neuronal circuits in freely moving mice affects acute and long-term behavior. This method is able to perform manipulations of ...

In vivo Optogenetic Stimulation of the Rodent Central Nervous System

The ability to probe defined neural circuits in awake, freely-moving animals with cell-type specificity, spatial precision, and high temporal resolution has been a long sought tool for neuroscientists in the systems-level search for the neural circuitry governing complex behavioral states. Optogenetics is a cutting-edge tool that is revolutionizing the field of neuroscience and represents one of the first systematic approaches to enable causal testing regarding the relation between neural signaling events and behavior. By combining optical and genetic approaches, neural signaling can be bi-directionally controlled through expression of light-sensitive ion channels (opsins) in mammalian cells. The current protocol describes delivery of specific wavelengths of light to opsin-expressing cells in deep brain structures of awake, freely-moving rodents for neural circuit modulation. Theoretical principles of light transmission as an experimental consideration are discussed in the context of performing in vivo optogenetic stimulation. The protocol details the design and construction of both simple and complex laser configurations and describes tethering strategies to permit simultaneous stimulation of multiple animals for high-throughput behavioral testing.

In vivo Optogenetic Stimulation of the Rodent Central Nervous System

Optogenetics has become a powerful tool for use in behavioral neuroscience experiments. This protocol offers a step-by-step guide to the design and set-up of laser systems, and provides a full protocol for carrying out multiple and simultaneous in vivo optogenetic stimulations compatible with most rodent behavioral testing paradigms.

在啮齿动物中枢神经系统的体内光遗传学刺激

The ability to probe defined neural circuits in awake, freely-moving animals with cell-type specificity, spatial precision, and high temporal resolution ...

神经科学

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings provide a sensitive approach to measure nerve conduction in humans and rodent models. To broaden the technical possibilities for electromyography in mice, the measurement of compound muscle action potentials (CMAPs) from the brachial plexus nerve in the forelimb using needle electrodes is described here. CMAP recordings after stimulating the sciatic nerve in hindlimbs have been previously described. The newly introduced method here allows for the evaluation of the nerve conductivity at an additional site, and thus provides a more profound overview of the neuromuscular functionality. The technique provides information on both the relative number of functional axons and the myelination level. Thereby, this method can be applied to assess both axonal diseases as well as demyelinating conditions. This minimally invasive method does not require extraction of the nerve and therefore it is suitable for repeated measurements for longitudinal follow-up in the same animal. Similar recordings are performed in clinical setups to emphasize the translational relevance of the method.

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration

The measurement of nerve conduction is a useful tool to assess mouse models of neurodegeneration but it is frequently only applied to stimulate the sciatic nerve in hindlimbs. Here, we describe a technique to measure compound muscle action potential (CMAP) in vivo in the mouse forelimb muscles innervated by the brachial plexus.

体内运动神经元变性小鼠前肢肌作用电位的电生理测量

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings ...

An Invasive Method for the Activation of the Mouse Dentate Gyrus by High-frequency Stimulation

Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for various neurological and psychiatric disorders. HFS in the deep region of the brain, also named deep-brain stimulation (DBS), is becoming increasingly important in clinical trials. Recent progress in the field of high-frequency DBS (HF-DBS) surgery has begun to spread the possibility of utilizing this invasive technique to other situations, such as treatment for major depression disorder (MDD), obsessive-compulsive disorder (OCD), and so on. 
Despite these expanding indications, the underlying mechanisms of the beneficial effects of HF-DBS remain enigmatic. To address this question, one approach is to use implanted electrodes that sparsely activate distributed subpopulations of neurons by HFS. It has been reported that HFS in the anterior nucleus of the thalamus could be used for the treatment of refractory epilepsy in the clinic. The underlying mechanisms might be related to the increased neurogenesis and altered neuronal activity. Therefore, we are interested in exploring the physiological alterations by the detection of neuronal activity as well as neurogenesis in the mouse dentate gyrus (DG) before and after HFS treatment. 
In this manuscript, we describe methodologies for HFS to target the activation of the DG in mice, directly or indirectly and in an acute or chronic manner. In addition, we describe a detailed protocol for the preparation of brain slices for c-fos and Notch1 immunofluorescent staining to monitor the neuronal activity and signaling activation and for bromodeoxyuridine (BrdU) labeling to determine the neurogenesis after the HF-DBS induction. The activation of the neuronal activity and neurogenesis after the HF-DBS treatment provides direct neurobiological evidence and potential therapeutic benefits. Particularly, this methodology can be modified and applied to target other interested brain regions such as the basal ganglia and subthalamic regions for specific brain disorders in the clinic.

This protocol shows how to set up a reliable HFS method in mice. Neurons throughout the hippocampal dentate gyrus are electrically stimulated by HFS directly and indirectly in vivo. Neuronal activity and molecular signaling are examined by c-fos and Notch1 immunofluorescent staining, respectively; neurogenesis is quantified by bromodeoxyuridine labeling assay.

高频刺激激活小鼠齿状回的侵袭方法

Electrical high-frequency stimulation (HFS), using implanted electrodes targeting various brain regions, has been proven as an effective treatment for ...

Transcranial Direct Current Stimulation (tDCS) in Mice

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for several neuropsychiatric diseases. The biological effects of tDCS are not fully understood, which is in part explained due to the difficulty in obtaining human brain tissue. This protocol describes a tDCS mouse model that uses a chronically implanted electrode allowing the study of the long-lasting biological effects of tDCS. In this experimental model, tDCS changes the cortical gene expression and offers a prominent contribution to the understanding of the rationale for its therapeutic use.

Transcranial Direct Current Stimulation tDCS in Mice

Transcranial direct current stimulation (tDCS) is a therapeutic technique proposed to treat psychiatric diseases. An animal model is essential for understanding the specific biological alterations evoked by tDCS. This protocol describes a tDCS mouse model that uses a chronically implanted electrode.

经颅直流电刺激 (tDCS) 在小鼠中的作用

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for ...

绘制脑血流和电场图:小鼠的电极放置

Placement of Extracranial Stimulating Electrodes and Measurement of Cerebral Blood Flow and Intracranial Electrical Fields in Anesthetized Mice

The detection of cerebral blood flow (CBF) responses to various forms of neuronal activation is critical for understanding dynamic brain function and variations in the substrate supply to the brain. This paper describes a protocol for measuring CBF responses to transcranial alternating current stimulation (tACS). Dose-response curves are estimated both from the CBF change occurring with tACS (mA) and from the intracranial electric field (mV/mm). We estimate the intracranial electrical field based on the different amplitudes measured by glass microelectrodes within each side of the brain. In this paper, we describe the experimental setup, which involves using either bilateral laser Doppler (LD) probes or laser speckle imaging (LSI) to measure the CBF; as a result, this setup requires anesthesia for the electrode placement and stability. We present a correlation between the CBF response and the current as a function of age, showing a significantly larger response at higher currents (1.5 mA and 2.0 mA) in young control animals (12-14 weeks) compared to older animals (28-32 weeks) (p &lt; 0.005 difference). We also demonstrate a significant CBF response at electrical field strengths &lt;5 mV/mm, which is an important consideration for eventual human studies. These CBF responses are also strongly influenced by the use of anesthesia compared to awake animals, the respiration control (i.e., intubated vs. spontaneous breathing), systemic factors (i.e., CO2), and local conduction within the blood vessels, which is mediated by pericytes and endothelial cells. Likewise, more detailed imaging/recording techniques may limit the field size from the entire brain to only a small region. We describe the use of extracranial electrodes for applying tACS stimulation, including both homemade and commercial electrode designs for rodents, the concurrent measurement of the CBF and intracranial electrical field using bilateral glass DC recording electrodes, and the imaging approaches. We are currently applying these techniques to implement a closed-loop format for augmenting the CBF in animal models of Alzheimer's disease and stroke.

作者聚焦:基于刺激的方法改善阿尔茨海默病模型中的脑血流 

We describe a protocol for assessing dose-response curves for extracranial stimulation in terms of brain electrical field measurements and a relevant biomarker-cerebral blood flow. Since this protocol involves invasive electrode placement into the brain, general anesthesia is needed, with spontaneous breathing preferred rather than controlled respirations.

麻醉小鼠颅外刺激电极的放置和脑血流量和颅内电场的测量

The detection of cerebral blood flow (CBF) responses to various forms of neuronal activation is critical for understanding dynamic brain function and ...

程控电刺激小鼠

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此视频中的章节

穿通通路 - 齿状回突触在自由活动的小鼠长时程增强

一个小鼠模型，通过神经肌肉电刺激肌肉训练

在小鼠的文室内使用光遗传学的两种不同的实时位置偏好范式

神经活性的光遗传学操作，调节自由移动小鼠的行为

在啮齿动物中枢神经系统的体内光遗传学刺激

体内运动神经元变性小鼠前肢肌作用电位的电生理测量

高频刺激激活小鼠齿状回的侵袭方法

经颅直流电刺激 (tDCS) 在小鼠中的作用

麻醉小鼠颅外刺激电极的放置和脑血流量和颅内电场的测量

麻醉小鼠颅外刺激电极的放置和脑血流量和颅内电场的测量