Name: microelectrode guided implantation of electrodes into the subthalamic nucleus of rats for long-term deep brain stimulation
Uploaded: 2015-10-02T15:00:00.000+00:00
Duration: 10 min 52 s
Description: Watch this Scientific Journal Video about Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation at JoVE.com

We wish to thank Mr Wabbel for preparing the wires and Mr Tietsch for constructing the plugs and cages according to our plans. This work was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 688). Felix Fluri holds a fellowship of the Interdisziplin&#228;re Zentrum f&#252;r Klinische Forschung (IZKF), University Clinics W&#252;rzburg, Germany.

动物实验批准了维尔茨堡大学和法治国家主管部门（下弗兰肯行政区，批准文号:54-2531.01-102 / 13）和执行根据的研究实验性卒中的建议，研究了17和当前的动物研究:的报告体内实验指南（http://www.nc3rs.org.uk/arrive-guidelines）。 1.麻醉<ol><li>检查麻醉剂系统，以确保供应气体（氧气）和异氟烷足量的过程的持续时间。连接的立体定位仪的门牙条鼻锥，把门牙栏上的-3.3毫米。 </li><li>打开供应气体（2L /分钟）。将大鼠成箱和密封的顶部。打开异氟烷蒸发器至3.5％。 </li><li>当老鼠是横卧，切换系统，使麻醉气体流到被固定到所述门齿杆鼻锥。 </li><li>删除RA吨从箱室和刮耳朵和眼睛之间的区域;用棉签浸泡Jodosept PVP，擦拭剃光区域，以消除任何松散的头发。 </li><li>定位在鼻锥（图1）的大鼠和继续用异氟烷2.5％麻醉中的 O 2（1升/分钟）。按捏叉指区域检查麻醉的水平。如果大鼠充分麻醉，防御反射被取消（脚即停药）。 </li><li>手术过程中监测呼吸和刺激反应，并根据需要调整蒸发器。 </li><li>取适量涂抹于眼兽医药膏，以防止干燥，而在麻醉下。监测和反馈控制的加热系统保持体温在37±0.5°C。 </li></ol> 2.手术<ol><li>保持术野消毒，整个手术过程中。一旦surgeon&#39;s手是无菌的并且操作字段是无菌的，只移动carefuLLY记得不要打破不育。这包括也是一个无菌区（ 即，无菌防水窗帘），哪一个可以放下工具。 </li><li>注入0.2 ml的甲哌卡因皮下进入剃区域的中心。甲哌卡因是局部麻醉剂具有至多3小时的作用持续时间。它会进一步麻醉手术区。 </li><li>使用手术刀，使两耳之间中线切口开始并朝向2厘米延伸。确保骨膜（皮肤下有光泽的膜）也被切开。暴露四个夹（ 图2）的头骨。 </li><li>用棉签，轻轻地取下骨膜，直到冠状面和矢状缝暴露;此后，止住血用脱脂棉。 </li><li>确定使用针固定在探头座前囟的坐标，然后标记针用黑色毡尖笔的尖端。使用前/后（AP）中线/外侧（ML）和背腹（DV）驱动螺丝，定位针的尖端直接在囟。 </li><li>参加AP和ML游标刻度读数:减去3.6毫米从AP的阅读和2.5毫米的ML读数电极植入右侧STN，或加入2.5毫米的电极植入左STN。针的尖端下降到颅骨的表面上后，此位置将被标记的毡尖笔的染料。 </li><li>夹紧牙钻到立体定位仪的大探头支架。将牙钻来计算的区域- 即，在头骨的标记点。看，通过显微镜，钻透头骨的孔（直径约1毫米），直到硬脑膜是可见的（头骨为约1毫米厚）。缩回使用显微解剖钳或消毒针头硬脑膜。硬脑膜是艰难的，足以摧毁电极的尖端。 </li><li>上钻孔，在每个正面鳞的牙钻，并且在整型erparietal相对的电极孔鳞。断开立体定位仪的探头支架。不要在颅骨缝钻的静脉血管遵循头骨下缝合。 </li><li>拧接骨螺钉到每一个五杆洞的。避免螺纹螺钉陷得太深。对于不锈钢螺丝（M1.6），2-3圈的螺丝将充分保持螺丝没有把压力对大脑。匝数取决于螺杆的螺距。夹紧探头支架具有（图3）中的显微电极。 </li><li>使用AP，ML和DV的驱动器螺钉，移动探头保持器与电极直到其前端几乎触及前囟。请注意AP，ML和DV游标刻度读数前囟门。当读数制成，提高电极几毫米以防止电极从运动期间刮头骨。为了确定位置的坐标，其中所述电极，必须在插洞口，增加3.6毫米到AP的阅读，并添加（或减）2.5mm至的ML阅读。 </li><li>使用AP和ML驱动螺丝，移动电极所计算的位置。在这一点上，电极尖端应当直接位于在钻孔电极孔。然后，通过查看通过显微镜，降低电极到硬脑膜（图4）的水平。这个水平作为零电平在DV方向。然后，轻轻地通过观察通过显微镜插入电极进入大脑的尖端。 </li><li>连接电极销到记录系统的连接器。放一个法拉第笼（或用铝箔代替它）在大鼠中的立体定位仪（图5）。接地立体定位仪与在正在处理房间的平衡。 </li><li>启动记录系统。如果有的话，还可以使用扬声器advancin过程中获得的排放/单台药膏的声信号克的电极。 </li><li>慢慢推进电极在录制过程中的电活动插入电极进入大脑。在距硬脑膜之间7.5和8.1毫米的深度，在STN的特定电活性通常是可检测的（图6）。在STN神经元的典型活性的特征在于不规则的点火模式和高的发射率（平均频率:40.9±12.9赫兹）18。 </li><li>在记录，减少尽可能麻醉（例如，0.8-1.0％）;低动物麻醉显示更清晰的电子大脑活动。 </li><li>拭远降低电极时被置换在颅骨的表面上的任何血液或脑脊液。 </li><li>混淆少量牙科水泥和应用它周围的电极及其周围的四个使用小刮铲（图7）的五个螺钉。第五螺钉将用于固定插头的接地线。 </li><li>断开记录系统的电极座和连接器的电极销，当牙科用粘固剂固定。 </li><li>拧开，这不是固定的牙科水泥螺丝。将电源插头上的电极针。固定与第五螺钉（图8）插头的接地线。 </li><li>混合了牙科水泥和运用它周围的插头。作为水泥变稠，模具它周围的插头，以形成一个盖。避免牙科水泥可能危害动物和硬化（ 图9A和 B）中删除它们锋利的边缘。 </li><li>清创伤口边缘和带缝线关闭它们的前部和所述盖的后面。消毒伤口边缘。 </li><li>头部插头连接到被固定在一个旋转的导线。从立体定位仪中取出老鼠。 </li><li>每日一次申请的曲马多（12.5毫克/千克，经腹膜内）在干预结束时，然后2-3天。放置老鼠在一个干净的笼THERMAl支持，固定在这个笼子（ 图10）旋转，仔细检查它1小时。 </li><li>不要让动物无人看管，直到它重新获得足够的意识，以保持胸骨斜卧。不返回已经历手术给其他动物的公司，直到完全恢复的动物。 </li></ol> 3.刺激<ol><li>确定使用阻抗计在动物的电阻刺激前。 </li><li>连接旋转的插头用导线和插头在导线与当前输出的另一端和用于刺激器的地线的输出。连接刺激与计算机，以便在节目的刺激器。 </li><li>选择刺激方案的参数;例如，在帕金森氏病中使用的参数是脉冲长度:60微秒;频率:130赫兹。与增加的电流幅值刺激老鼠，直至运动障碍的认可。减少日电子电器强度由强度低于10-20％是引起运动障碍，或直至神经症状消失，所述动物是舒适。单相矩形脉冲在此研究中使用。 </li><li>在完成实验后，安乐死用异氟烷动物:调整isofurane流量或浓度为5％或更大。继续异氟醚曝光，直至呼吸停止后1分钟。 </li></ol>

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The authors declare that they have no competing financial interests.

<html>这项研究提出了一个一步一步的指令集，用于植入单极慢性电极插入老鼠的STN。虽然具有低阻抗钨电极通常用于DBS 18,19，由铂/铱（铂/铱）溶液采用该具有约1兆欧的阻抗的单极电极。铂/铱电极也可用于治疗帕金森氏病，因为它们的有利性质的:它们显示最低侵蚀20，不产生，如果没有高的电荷密度被用于相关组织损伤21。由于本研究的目的是一个长期刺激设置和，以达?...

深部脑刺激（DBS）是一种基于电脉冲通过植入电极，以特定脑结构中，递送一个治疗诸如内部苍白球1，底丘脑核（STN）2 - 4或腹侧中间丘脑5。在过去的二十年中，这种治疗方法已经被确立为一个有力的治疗工具为帕金森氏病1 - 4，张力障碍6和震颤7，并且也用于调节慢性疼痛7，精神障碍（例如，强迫症8，抑郁症9）或难治性癫痫10,11。此外，DBS可能，在未来，成为耐火动脉高血压12或体位性低血压13一种治疗选择。 效果背后的生理机制DBS的仍然知之甚少。在研究啮齿动物的麻醉提供了深入了解，以模仿临床应用DBS 14高频刺激神经 ​​反应。然而，这些研究不仅缺乏的DBS影响行为的佐证，但也导致依赖于刺激参数相当大的变化应用14。 为了研究更简明星展银行在有意识的啮齿类动物行为的影响和作用机制，刺激建立是必要的，满足特定需求。 DBS大多用作长期治疗（例如，帕金森氏病，慢性疼痛）。因此，刺激设置在啮齿类动物的设计应使该单元由一个插头，以及从插头向外部刺激器的导线的电极的;当固定在头骨这个单位应该是轻量级的，但牢不可破。此外，行动自由是必不可少的stimula在大鼠化过长时间。 DBS的目标结构是小的;例如，在大鼠中的STN的长度为1.2毫米和0.8毫米3,15的体积。因此，电极必须被设计为使得细胞核未插入时损伤并靶向需要是精确的。如在啮齿类动物进行最DBS研究已经使用的电极与靶结构基础的里程碑式的立体定向插入时，错误率可以是比较高的，根据Paxinos和Watson 16使用坐标时也是如此。这导致达到统计学上有意义的结果需要的动物的数量较多。 在本研究中的电极注入技术被引入，即通过使用一个microrecording系统，同时推进电极靶向以高精度在STN。此外，刺激系统，提出不仅允许移动性的刺激动物的高度，而且确保连续stimulati上通过的刺激导线的安全固定（这是由一个不锈钢弹簧保护）到大鼠的头部。

<table><tbody><tr><td>Pt/Ir electrode</td><td>FHC Inc.</td><td>UE</td><td>Custom-made: Specification: UEPSEGSECN1M</td></tr><tr><td>Plugs</td><td>GT Labortechnik (Arnstein/Germany)</td><td></td><td>Custom-made</td></tr><tr><td>Pin header</td><td>DISTRELEC</td><td>143-95-324</td><td>single-row, 90&amp;deg; 1x3 datamate, Type M80-8420342</td></tr><tr><td>Socket</td><td>DISTRELEC</td><td>143-95-621</td><td>single-row,straight 2 mm pole no.1 x 3 datamate, Type M80-8400342</td></tr><tr><td>Stainless steel spring</td><td>Plastics ONE</td><td>SS0102</td><td>Part-#: .120 X .156 Spring ID (mm): 3.0&amp;nbsp; Spring OD (mm): 4.0</td></tr><tr><td>Dental cement/Paladur</td><td>Heraeus Kulzer</td><td>64707938</td><td>Liquid, 500 ml</td></tr><tr><td>Dental cement/Paladur</td><td>Heraeus Kulzer</td><td>64707954</td><td>Powder, rose, 500 g</td></tr><tr><td>Head screw</td><td>Hummer &amp;amp; Reiss</td><td>V2ADIN84 M1.6x3</td><td></td></tr><tr><td>Jodosept PVP</td><td>Vetoquinol</td><td></td><td>435678/E04</td></tr><tr><td>Mepivacain 1%</td><td>AstraZeneca</td><td></td><td>PZN03338515</td></tr><tr><td>Epinephrine</td><td>Sanofi-Aventis</td><td></td><td>PZN00176118</td></tr><tr><td>Tramadolhydrochloride</td><td>Rotexmedica</td><td></td><td>38449.00.00</td></tr></tbody></table>

microelectrode guided implantation of electrodes into the subthalamic nucleus of rats for long-term deep brain stimulation

深部脑刺激（DBS）是一种广泛使用的和有效的疗法为几个神经系统疾病，例如特发性帕金森氏病，肌张力障碍或震颤。 DBS是基于递送电刺激中枢神经系统的特定深解剖结构。不过，DBS的效果背后的机制仍然是神秘的。这导致了兴趣调查DBS的在动物模型中的影响，特别是在大鼠。作为星展是一个长期的治疗，研究应集中在星展银行之后发生的数周神经回路的分子遗传学改变。长期DBS在大鼠是具有挑战性的，因为老鼠走动的笼子里，这将导致在保持到位，从动物到刺激的头部领先的电线问题。此外，靶结构刺激大鼠脑内都很小，因此电极不能很容易地放置在所要求的位置上。因此，设置为长效stimula使用铂/铱电极具有大约1兆欧的阻抗大鼠和灰这项研究开发的。这些规范的电极不仅允许足够的刺激，也记录脑深部结构，以确定目标区域的DBS。在我们的设置，用塞子为电线的电极包埋在牙科用粘固剂与固定在颅骨4锚固螺钉。从插头到刺激器的导线是由一个不锈钢弹簧保护。旋转接头被连接到电路，以防止电线的缠结。总体而言，这种刺激设置提供自由流动的高度为大鼠和使头部插头，以及在插头和刺激器之间的导线连接，以保持持久的强度。

植入电极插入用的记录系统大鼠的STN - 作为这里提出 - 是一种有效和精确的程序的DBS该取每只动物约1小时。这个模型是一个相当小的过程:10只进行手术，全部存活的干预。介入后二十四小时，将每只大鼠的状态进行监测，并没有动物根据严重码实现了超过1的3个点。在连续刺激（14天，24小时的天）期间，没有电线脱落，破裂或被咬伤过。没有一个10只失去牙科水泥盖也没有他们得到由设备过程中...

Watch this Scientific Journal Video about Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation at JoVE.com

Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

微电极引导电极植入到大鼠丘脑底核的长期深部脑刺激

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, ...

microelectrode-guided-implantation-electrodes-into-subthalamic

Universidad de Cartagena UDEC

Research

JoVE Journal

Neuroscience

19.5K 次观看.  University Hospital Wuerzburg. A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

视频: Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor 1. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials 2. Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. 
DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation 3. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity 4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

在接受深部脑刺激手术术中唤醒人类行为任务

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through ...

科研

医学

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

一般方法评估对静脉注射甲基苯丙胺的自我管理深部脑刺激的影响

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

行为学

Surgical Implantation of Chronic Neural Electrodes for Recording Single Unit Activity and Electrocorticographic Signals

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery. Here we provide useful information for surgeons who are learning the process of implanting electrode systems. We demonstrate the implantation procedure of both a penetrating and a surface electrode. The surgical process is described from start to finish, including detailed descriptions of each step throughout the procedure. It should also be noted that this video guide is focused towards procedures conducted in rodent models and other small animal models. Modifications of the described procedures are feasible for other animal models.

We provide useful information for surgeons who are learning the process of implanting chronic neural recording electrodes. Techniques for both penetrating and surface electrode systems are described in a rodent animal model.

用于记录单机活动和Electrocorticographic信号的慢性神经电极植入手术

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery.  Here we provide useful information for ...

神经科学

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal&#180;s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

A wireless, bidirectional system for multi-channel neural recordings and stimulation in freely behaving rats is introduced. The system is light and compact, thus having minimal impact on the animal&#180;s behavioral repertoire. Moreover, this bidirectional system provides a sophisticated tool to assess causal relationships between brain activation patterns and behavior.

用于体内的无线双向接口记录和刺激自由行为大鼠的神经活动

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.&#160;Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.

This protocol describes a standard method for simultaneous functional magnetic resonance imaging and deep brain stimulation in the rodent. The combined use of these experimental tools allows for the exploration of global downstream activity in response to electrical stimulation at virtually any brain target.

深部脑刺激与同步功能磁共振成像在鼠害

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective treatment for several movement disorders that have failed to respond to medication. Recent progress in the field of DBS surgery has begun to extend the application of this surgical technique to other conditions as diverse as morbid obesity, depression and obsessive compulsive disorder. Despite these expanding indications, little is known about the underlying physiological mechanisms that facilitate the beneficial effects of DBS surgery. One approach to this question is to perform gene expression analysis in neurons that receive the electrical stimulation. Previous studies have shown that neurogenesis in the rat dentate gyrus is elicited in DBS targeting of the anterior nucleus of the thalamus1. DBS surgery targeting the ATN is used widely for treatment refractory epilepsy. It is thus of much interest for us to explore the transcriptional changes induced by electrically stimulating the ATN. In this manuscript, we describe our methodologies for stereotactically-guided DBS surgery targeting the ATN in adult male Wistar rats. We also discuss the subsequent steps for tissue dissection, RNA isolation, cDNA preparation and quantitative RT-PCR for measuring gene expression changes. This method could be applied and modified for stimulating the basal ganglia and other regions of the brain commonly clinically targeted. The gene expression study described here assumes a candidate target gene approach for discovering molecular players that could be directing the mechanism for DBS.

The mechanism underlying the therapeutic effects of Deep Brain Stimulation (DBS) surgery needs investigation. The methods presented in this manuscript describe an experimental approach to examine the cellular events triggered by DBS by analyzing the gene expression profile of candidate genes that can facilitate neurogenesis post DBS surgery.

基因表达的变化大鼠海马后，前丘脑核脑深部刺激分析

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective ...

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a closed-loop event-triggered manner. Although many studies are focusing on the possible benefits and side-effects of TES in healthy and pathologic brains, there are still many fundamental open questions regarding the mechanism of action of the stimulation. Therefore, there is a clear need for a robust and reproducible method to test the acute and the chronic effects of TES in rodents. TES can be combined with regular behavioral, electrophysiological, and imaging techniques to investigate neuronal networks in vivo. The implantation of transcranial stimulation electrodes does not impose extra constraints on the experimental design while it offers a versatile, flexible tool to manipulate brain activity. Here we provide a detailed, step-by-step protocol to fabricate and implant transcranial stimulation electrodes to influence brain activity in a temporally constrained manner for months.

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

大鼠慢性经颅电刺激及 Intracortical 记录

Transcranial electrical stimulation (TES) is a powerful and relatively simple approach to diffusely influence brain activity either randomly or in a ...

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 ...

Subdural Soft Electrocorticography (ECoG) Array Implantation and Long-Term Cortical Recording in Minipigs

Neurological impairments and diseases can be diagnosed or treated using electrocorticography (ECoG) arrays. In drug-resistant epilepsy, these help delineate the epileptic region to resect. In long-term applications such as brain-computer interfaces, these epicortical electrodes are used to record the movement intention of the brain, to control the robotic limbs of paralyzed patients. However, current stiff electrode grids do not answer the need for high-resolution brain recordings and long-term biointegration. Recently, conformable electrode arrays have been proposed to achieve long-term implant stability with high performance. However, preclinical studies for these new implant technologies are needed to validate their long-term functionality and safety profile for their translation to human patients. In this context, porcine models are routinely employed in developing medical devices due to their large organ sizes and easy animal handling. However, only a few brain applications are described in the literature, mostly due to surgery limitations and integration of the implant system on a living animal.
Here, we report the method for long-term implantation (6 months) and evaluation of soft ECoG arrays in the minipig model. The study first presents the implant system, consisting of a soft microfabricated electrode array integrated with a magnetic resonance imaging (MRI)-compatible polymeric transdermal port that houses instrumentation connectors for electrophysiology recordings. Then, the study describes the surgical procedure, from subdural implantation to animal recovery. We focus on the auditory cortex as an example target area where evoked potentials are induced by acoustic stimulation. We finally describe a data acquisition sequence that includes MRI of the whole brain, implant electrochemical characterization, intraoperative and freely moving electrophysiology, and immunohistochemistry staining of the extracted brains.
This model can be used to investigate the safety and function of novel design of cortical prostheses; mandatory preclinical study to envision translation to human patients.

Subdural Soft Electrocorticography ECoG Array Implantation and Long-Term Cortical Recording in Minipigs

Here, we present a method for the long-term performance and safety assessment of soft subdural electrode arrays in a minipig model, describing surgical method and tools, postoperative magnetic resonance imaging, electrophysiology of the auditory cortex, electrochemical properties of the implant, and postmortem immunochemistry.

硬膜下软皮质电图 （ECoG） 阵列植入和小型猪的长期皮质记录

Neurological impairments and diseases can be diagnosed or treated using electrocorticography (ECoG) arrays. In drug-resistant epilepsy, these help ...

生物工程

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Source: Melo-Thomas, L., et al., <a href="https://appjove.unicartagenaproxy.elogim.com/v/56299">A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats.</a> J. Vis. Exp. (2017)
The video demonstrates a procedure for implanting a wireless bidirectional multichannel electrode unit into a rat brain to record and stimulate multichannel neural networks.

在大鼠大脑中植入无线双向微电极系统

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
1. ...

微电极引导电极植入到大鼠丘脑底核的长期深部脑刺激

摘要

探索更多视频

此视频中的章节

在接受深部脑刺激手术术中唤醒人类行为任务

一般方法评估对静脉注射甲基苯丙胺的自我管理深部脑刺激的影响

用于记录单机活动和Electrocorticographic信号的慢性神经电极植入手术

用于体内的无线双向接口记录和刺激自由行为大鼠的神经活动

深部脑刺激与同步功能磁共振成像在鼠害

基因表达的变化大鼠海马后，前丘脑核脑深部刺激分析

大鼠慢性经颅电刺激及 Intracortical 记录

高频刺激激活小鼠齿状回的侵袭方法

硬膜下软皮质电图（ECoG）阵列植入和小型猪的长期皮质记录

在大鼠大脑中植入无线双向微电极系统

微电极引导电极植入到大鼠丘脑底核的长期深部脑刺激

摘要

探索更多视频

此视频中的章节

在接受深部脑刺激手术术中唤醒人类行为任务

一般方法评估对静脉注射甲基苯丙胺的自我管理深部脑刺激的影响

用于记录单机活动和Electrocorticographic信号的慢性神经电极植入手术

用于体内的无线双向接口记录和刺激自由行为大鼠的神经活动

深部脑刺激与同步功能磁共振成像在鼠害

基因表达的变化大鼠海马后，前丘脑核脑深部刺激分析

大鼠慢性经颅电刺激及 Intracortical 记录

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