Name: surgical training for the implantation of neocortical microelectrode arrays using a formaldehyde-fixed human cadaver model
Uploaded: 2017-11-19T13:00:00.000+00:00
Duration: 8 min 11 s
Description: Watch this Scientific Journal Video about Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model at JoVE.com

作者感谢 Dr. 罗布 (贝莱德微计算机系统), Prof. Margitta Seeck (神经内科, 日内瓦大学医院, 日内瓦, 瑞士), Dr. 安德烈巴托丽和 Prof. 卡尔夏勒 (日内瓦大学神经外科司医院, 日内瓦, 瑞士), 和 Mr. 马卢达 Burdin 和 Prof. 约翰 p o'donoghue (Wyss 中心为生物和神经, 日内瓦, 瑞士) 为他们的支持在准备当前工作。

这项工作中使用的人体尸体是在医学教育的身体捐赠框架下提供的。捐赠者在世时以书面形式获得了对遗体捐献的知情同意书。根据联邦和州的法律, 没有必要对道德委员会进行审查。
注: 本协议假设, 执行手术的人外科的训练和专业知识的标准神经外科程序, 包括病人定位和头部固定, 开颅和 durotomy, 缝合。除了专用于微电极阵列的工具和设备外, 还使用标准的神经外科工具和设备。
1. 选择尸体和设置手术室
<ol><li>选择一个没有疾病史或头部、头骨和大脑损伤的标本。<ol>
<li>(可选) 对尸体头部进行计算机断层扫描 (CT) 检查, 以确保没有明显的颅内病变 (图 1A), 如慢性硬脑膜下血肿或 intra-axial 扩张性病变。使用 CT 扫描, 确定一个靶皮层区的微电极阵列植入 (如 "手旋钮" 区域的中央回, 对应于手的表示在主电机皮层27, 在训练的情况下用于植入一个接口)。</li>
	</ol>
</li>
	<li>将尸体放在手术台的侧面卧位。使用手术台, 而不是解剖表, 以增加现实主义的或类似的环境, 并促进固定的头骨钳和气动冲击器。将尸体放置在侧卧位, 以便在一个甲醛固定的尸体上允许额时间的方法, 其中颈部旋转是有限的。</li>
	<li>将头部固定在颅骨钳上 (图 1B)。用手术窗帘覆盖 (图 1C)。 注意: 在我们的情况下, 头骨钳的后针在头部的矢状面上异常地定位 (参见图 1B), 因为我们使用了一个头骨钳, 它已被修改为外科训练目的, 以保存与其余部分分离的尸体头。的身体。<ol>
<li>当使用一个标准的头骨钳在手术台上, 放置后针固定头部垂直于矢状面。</li>
	</ol>
</li>
</ol>2. 皮层表面的曝光
<ol><li>用手术刀切开头皮, 在一个问号切口后, 露出颞侧和额骨。解剖沿切口后缘的颞肌。通过钝解剖 (图 1D) 将头皮和颞肌肉倾斜。</li>
	<li>进行大面积的额颞开颅手术, 例如 5 x 5 厘米 (图 2A)。为此, 在预定的开颅的拐角处钻出四毛刺孔。然后, 使用 craniotome 连接毛刺孔。用刮刀取出骨瓣, 露出硬脑膜。将骨瓣储存在盐水溶液中。</li>
	<li>用硬脑膜剪刀 (图 2B) 打开开颅三侧的硬脑膜。倾斜它, 露出蛛网膜和大脑皮层的表面 (图 2C)。</li>
</ol>3. 电极基座固定
<ol><li>选择一个皮质回, 其中微电极阵列将被植入。选取一个近似平坦的回转窑曲面, 使微电极阵列在插入时会与它齐平。确保在皮质表面上没有可见的血管在微电极阵列上入。</li>
	<li>选择一个固定在开颅的上边缘的电极基座的位置, 靠近皮肤切口, 并允许足够松弛的电线束, 使微电极阵列可以达到目标回。螺钉的基座上的头骨骨旁边的开颅 (图 2D) 的外部表。使用6至8攻皮质骨螺钉 (6 毫米长度, 2 毫米直径), 以确保适当的固定。<ol>
<li>在操纵基座时, 一定要确保微电极阵列不触及任何物体 (它可能被损坏或可能划破皮层表面), 它通过用镊子和塑料钳将线束紧紧地握在电极阵列上。橡胶涂层的提示 (图 2E)。</li>
	</ol>
</li>
</ol>4. 微电极阵列的定位和插入
<ol><li>将微电极阵列与靶回的表面平行放置。根据需要为该用途弯曲线束 (图 3A)。 注意: 硬线束不容易符合外科医生的意愿。需要细心和耐心才能使微电极阵列和皮质表面得到良好的对准。<ol>
<li>(可选) 使用 "狗骨" 钛带, 确保线束固定在头骨上, 并控制其朝向靶脑回的过程。不要把皮带拧得太紧, 以免损坏电线束。</li>
	</ol>
</li>
	<li>使气动冲击器与微电极阵列的背面近似对准 (图 3B)。控制气动冲击器与控制箱的连接, 然后打开控制箱。 注: 在打开控制箱之前, 确保气动冲击器至少离阵列5毫米, 因为在第一次打开时可能会触发气压冲击。</li>
	<li>使用气动冲击器的毫米螺钉, 用微电极阵列的背面 (图 3B, 嵌入) 来细化撞击者的对准。使用撞击器, 在微电极阵列的背面应用一个漂移距离和压力控制的水龙头, 并将其插入皮层表面, 将其推入蛛网膜。 注: 检查微电极阵列是否与皮质表面齐平。</li>
</ol>5. 硬膜下 ECOG 网的定位
注意: 此步骤是可选的。
<ol><li>将硬膜下 ECOG 网格置于裸露的皮质表面 (图 3D)。如有必要, 通过切割栅格来去除电极, 使 ECOG 网格的整体形状适合开颅。</li>
	<li>ECOG 格栅, 使其电线将退出硬脑膜和头骨的优越或向后。</li>
	<li>用盐水冲洗 ECOG 网格, 然后再将其与皮质表面接触。</li>
	<li>通过缝合到 durotomy 边缘的硬脑膜, 确保 ECOG 网格的安全。</li>
</ol>6. 硬脑膜、骨瓣和皮瓣的复位和闭合
<ol><li>反射硬脑膜背部暴露的皮质表面和缝合到边缘的 durotomy。</li>
	<li>螺丝 "狗骨" 钛带上的边缘骨瓣使用攻皮质骨螺钉。在开颅手术中重新定位骨瓣。用 "狗骨" 钛带和攻皮质骨螺钉将骨瓣固定到相邻的颅骨骨上。注意不要粉碎微电极阵列 (和可选 ECOG 网格) 的线束在骨骼边缘之间。</li>
	<li>反射和缝合皮瓣。关闭在电极底座 (图 3E) 的颈部周围的皮肤切口。<ol>
<li>另外, 允许基座通过一个单独的刺切口进入头皮皮瓣。</li>
	</ol>
</li>
</ol>

作者没有什么可透露的。

甲醛固定的人体尸体模型和手术协议描述复制的外科手术过程中植入微电极阵列到人脑皮质。该过程的每一步, 包括微电极阵列的定位和它的插入与气动插入, 进行几乎相同的方式在现实生活中的病人, 除了脑搏动和循环缺席。该协议中的关键步骤是将微电极阵列与皮层表面对齐, 并使用气动插入将其撞击到皮层。必须注意将该阵列近似为与皮质表面平行的可能性。在这种情况下, 该阵列不说谎冲洗与皮层表面后, 第一次水龙头的气动插入, 一个额外的水龙头可以交付。在整个过程中, 应保护微电极阵列不受机械损伤。如果在病人的临床条件下植入, 如果对电极、捆绑或连接器有任何明显的损伤, 则应丢弃该阵列, 并使用另一组。
犹他州阵列是目前唯一的皮层微电极阵列, 已经得到了在人类使用的监管批准。然而, 其他类型的电极已开发的动物, 并可用于人类在特定的研究项目28。每种方法都有其自身的优缺点, 主要与电极的设计有关。例如, 犹他州阵列的弹道插入技术是出于必要的25而开发的, 它要求阵列与皮层表面精确对准;这一要求不一定适用于其他电极, 它可以被轻轻地推入灰色物质。一些电极允许进入所有皮层层的活动29, 而犹他阵列则是在一个单一的, 预定深度的神经元样本。犹他州阵列的主要优势之一是可以同时记录的大量神经元, 这使得它特别适合于电机 BCIs11。
对于神经外科实验室的训练课程, 尸体标本被认为是高价值的模型, 允许在一个环境中的触觉反馈, 特别是人体解剖学30,31。没有普遍的尸体模型, 但是, 防腐技术必须适应每个程序的目标: 是软组织 (如头皮) 的重要性, 或更确切地说, 骨骼, 硬脑膜, 皮质, 脑室, 或血管32, 33、34、35、36？新鲜或新鲜冰冻 (冷冻) 标本, 而经常被认为是最好的模式, 为各种手术程序, 承担传播传染病的风险。此外, 他们有一个非常有限的工作时间, 因为快速衰减31,37,38,39, 随后减少组织依从性, 心室塌陷和性35. 在我们的协议的情况下, 保持一个有点坚定的皮层表面是一个要求, 使插入的微电极阵列, 从而排除使用的新鲜冷冻标本。防腐解决方案提供长期的定影和杀菌性能也被广泛接受30,33,35,40。尸体防腐根据泰尔固定是高度重视软组织的一致性和发展筋膜或 internervous 飞机36, 但大脑的保存被认为缺乏现实主义的41。Formaldehyde-based 固定导致组织僵硬和缩回以及变色35,36,37。然而, 甲醛固定是广泛可用和负担得起的, 甲醛固定的尸体是非常耐用的。在本文所介绍的背景下, 由甲醛固定引起的软组织硬化, 虽然是许多外科训练课程 (特别是矫形方法) 的缺点, 结果是一个适当的模型, 呈现出一个稳定的,但不太僵硬的大脑表面, 从而允许一个现实的应用皮质微电极阵列在死后脑。为模拟血液和脑脊液在甲醛固定尸体中的循环而开发的技术30,31,39 , 并可以补充本协议以进一步增加现实主义的或类似的环境。
三维 (3D) 印刷最近已成为一个可获得和负担得起的手段复制身体部件的医疗和外科教育。新颖的3D 印刷和成型使用合成胶质石膏提供了一个现实的大脑模型与触觉反馈。这种方法的优势是提供一个可变形结构, 可以打印, 以重现一个特定的人的大脑解剖, 因此更具有解剖学上的准确性比一般模型42。另一方面, 对合成材料的刚度和组织切割性能的影响还是有保留的43。从这个意义上说, 尸体模型提供了一个更广泛的解剖框架, 包括完整的地层, 不仅是大脑表面本身。
在人类尸体上进行外科训练的另一种方法是在活体动物上练习。在灵长类动物模型上植入微电极阵列, 例如一只猕猴, 将再现人类病人实际手术过程的大部分特征, 包括与人类使用的外科定位和仪器,gyrencephalic 大脑的大小与人类的不太远, 脑搏动的存在以及血液和脑脊液循环。然而, 尽管在猴子中植入微电极阵列以进行神经科学研究是可以接受的, 但由于伦理原因以及高昂的成本, 只用猴子进行外科训练是很普遍的。因为很少有神经科学中心在猴子体内植入微电极阵列用于研究目的, 而且因为这些中心一次只使用少量的动物 (由于猴子本身的成本和长期和 labor-intensive 的训练, 神经科学研究与猴子一般需要), 在猴子的微电极阵列植入训练不是大多数外科医生的选择。使用较小的动物, 如啮齿动物, 甚至猫或兔子, 会偏离太多或类似的现实主义。动物模型的一个潜在的好处是组织愈合允许在动物的一生中重复整个过程不止一次。在人类尸体模型中, 整个过程可以在每个半球重复一次。据说, 开颅手术并没有给训练有素的神经外科医生提出任何特别的困难。如果开颅手术足够大, 那么在特定的时段内, 可以在一定的时间内重复进行支架固定和微电极定位和插入的具体步骤, 为不止一个外科医生提供足够的训练机会。因此, 我们认为, 经过防腐的人体尸体是培养外科医生植入微电极阵列的最合适的模型。
最近在脑机的发展方面的突破表明, 微电极阵列可以代表一个临床上显著增加的治疗和恢复解决方案, 现在可用于严重运动或沟通障碍患者11,13,44. 在不久的将来, 微电极阵列的植入可能因此成为外科训练的必要部分。改进的电极本身的设计, 连同改善连接电极的计算机处理神经元信号 (可能通过无线连接), 将减少微电极阵列的侵袭性和进一步提高医生和病人及其照顾者的可用性。

近年来, 在活体脑中记录多个单个神经元活动的挑战的技术解决方案的发展1,2,3。硅基微电极阵列在信号特性方面与传统的线电极相似, 它们可以在脑组织的小片中记录几十到数百个神经元4,5,6,7. 微电极阵列使科学家们能够在猴子的初级运动皮层和手臂运动之间建立神经活动的对应关系,8, 这反过来又为脑机的发展提供了推动力。接口 (BCIs)9。
微电极阵列已被用于人类在两种情况下: 作为慢性植入物控制 BCIs 和作为 semi-chronic 植入物, 研究的活动的个别神经元的病人患有癫痫。慢性植入物, 以手的功能表示为目标在主要马达皮层, 允许患者遭受四肢控制机器人胳膊或计算机游标的运动10,11,12 ,13。半慢性植入物, 连同硬膜下脑电图 (ECOG) 电极插入与耐药癫痫患者谁是癫痫手术的候选者14, 允许单录音之前, 期间和之后癫痫发作,并已开始阐明癫痫发作期间和期间单个神经元的活动15,16,17,18,19。微电极阵列有可能显著提高我们对大脑功能的认识, 通过建立神经元活动之间的联系, 以及人类的感知、运动和思想, 无论是在健康方面还是在疾病, 在其他20,21。
硅基微电极阵列现已商业化, 其在人类中的使用已被美国的监管当局批准在 semi-chronic 癫痫征兆。然而, 这些设备是侵入性的, 必须插入到大脑中。不适当的插入技术的消极后果, 除了设备的失败记录神经元活动, 包括脑出血和感染, 潜在的长期或永久性的神经功能障碍。尽管目前尚不清楚微电极阵列植入术的并发症率, 但颅内脑电图 (EEG) macroelectrodes 的潜在严重并发症发生率为 1-5%22,23. 因此, 正确植入微电极阵列需要广泛的神经外科技术和特定的程序训练。
在安全的环境中, 外科医生用微电极阵列来磨练技能的方法包括非人类哺乳动物和人体尸体。理想的训练模式将忠实地再现人类头骨的大小和厚度;硬脑膜的韧性和血管衍生物;人脑的 gyrification 模式、一致性和脉动;循环血和脑脊液的存在;以及主体在手术室 (或) 类似环境中的整体定位。因此, 动物模型需要有足够的规模, 为外科医生提供有意义的经验。大型非人灵长类动物最接近, 但他们的外科训练的使用是不可持续的, 从伦理的角度来看, 因为它们是昂贵的。啮齿目动物不进入考虑由于他们的小大小;即使是猫或兔子, 也意味着从一个或类似的环境中明显地发散。
人类的尸体代表着一个诱人的选择他们的优势包括生命样的大小和头部和大脑的形状和在一个或类似的环境中建立外科训练的可能性。最明显的离开从现实的情况是没有脑脉动和出血, 并修改的方面和一致性的身体组织, 是专门为尸体保存的技术24。新鲜冷冻的尸体在某种程度上保持了许多器官和组织的一致性和灵活性, 但它们有几个缺点: 一旦解冻开始, 它们就开始降解, 从而使大脑变得过于退化, 无法插入微电极阵列要现实地执行, 它们是一种相对稀少且昂贵的资源。而甲醛固定的尸体, 另一方面, 是更实惠, 可用和更耐用, 以牺牲硬化组织的一致性。
在这里, 我们建立了一个程序使用甲醛固定的人体模型, 提供神经外科训练的植入皮层微电极阵列。我们的方法允许现实的, 或类似的定位和仪器;进行开颅和 durotomy, 暴露皮层表面;将电极基座连接到颅骨骨周围的开颅;用气动冲击器25将微电极阵列插入到大脑皮层中。重要的是, 它使外科医生能够实践的精确对准的微电极阵列 (这是连接到电极基座由一捆单独绝缘金丝) 平行的皮层表面26。我们的协议忠实地复制的迹象, 微电极阵列植入和 ECOG 植入的病人谁是癫痫手术的候选者。微电极阵列的精确类型对植入手术的特殊性有显著影响;在这里, 我们描述了一个数组的程序, 最近得到了在美国使用的监管批准。so-called 犹他阵列包括一个4x4 毫米, 100 微电极网格;附着在颅骨外表上的经皮底座;和连接两个的线束。

<table><tbody><tr><td>Mayfield skull clamp</td><td>Integra LifeSciences, Cincinnati, OH</td><td>A1059</td><td></td></tr><tr><td>Midas Rex MR7 system for craniotomy</td><td>Medtronic, Minneapolis, MN</td><td>EC300</td><td></td></tr><tr><td>Dura scissors</td><td>Sklar Surgical Instruments, West Chester, PA</td><td>22-2742</td><td></td></tr><tr><td>Self-tapping bone screws</td><td>OrthoMed Inc., Tigard, OR</td><td>OM SYN211806</td><td></td></tr><tr><td>Microelectrode array and pedestal</td><td>Blackrock Microsystems, Salt Lake City, UT</td><td>LB-0612</td><td>Mock-up arrays are available from the manufacturer upon request</td></tr><tr><td>Pneumatic impacter</td><td>Blackrock Microsystems, Salt Lake City, UT</td><td>LB-0088</td><td></td></tr><tr><td>64-channel electrocorticography grid</td><td>Ad-Tech Medical Instrument Corporation, Racine, WI</td><td>FG64C-SP10X-0C6</td><td>Optional</td></tr></tbody></table>

surgical training for the implantation of neocortical microelectrode arrays using a formaldehyde-fixed human cadaver model

本议定书描述了一个程序, 以协助外科医生在训练植入微电极阵列到人脑的大脑皮层。最近的技术进步使制造的微电极阵列, 使记录的活动, 多个单独的神经元在大脑皮层的人脑。这些阵列有可能带来独特的洞察力的神经元关联的大脑功能的健康和疾病。此外, 意志神经元活动的识别和解码打开了建立脑机接口的可能性, 从而有助于恢复失去的神经功能。皮层微电极阵列的植入是一种侵入性的手术, 需要超 centimetric 开颅和皮质表面的暴露;因此, 该程序必须由训练有素的神经外科医生执行。为了提供一个外科训练的机会, 我们设计了一个基于人体尸体模型的程序。使用甲醛固定的人类尸体绕过了动物 (特别是非人灵长类) 外科手术的实际、伦理和财政困难, 同时保持头部、头骨、脑膜和脑的宏观结构表面和允许逼真, 操作室式定位和仪表。此外, 人类尸体的使用比任何非人类模型更接近临床的日常实践。尸体模拟的主要缺点是缺乏脑搏动和血液和脑脊液循环。我们建议, 一个甲醛固定的人体模型是一个适当的, 切实可行的和 cost-effective 的方法, 以确保适当的外科训练前植入微电极阵列在活体人类大脑皮层。

我们的协议使用了一种甲醛固定的人体模型, 让外科医生能够在现实的或类似的环境中, 实施将微电极阵列植入大脑大脑皮层的手术方法。进行后验神经影像的选择, 如头颅 CT, 将证实没有任何重大颅内病变 (图 1A), 并可以帮助选择植入部位。使用整个标本并在手术台上进行手术, 这增加了训练过程的真实性 (图 1B-1C)。虽然甲醛固定有一定程度上改变了身体组织的颜色、质地和硬度, 但每一个手术步骤暴露皮层表面 (皮肤切口、开颅和 durotomy) 都可以根据标准轻松执行神经外科练习 (图 1D和图 2A-2C)。
特定于微电极阵列的外科手术步骤与体内情况非常相似。第一步包括拧紧电极基座到颅骨骨附近的开颅手术 (图 2D-2E)。使微电极阵列与皮层表面对齐是过程中最微妙的步骤之一 (图 3A)26。气动冲击器的定位和操作也以逼真的方式进行 (图 3B)。我们的训练方案为外科医生提供了充分的机会来试验这些关键步骤。一个离开逼真的现实主义是没有大脑脉动的尸体模型 (轻微向上和向下运动暴露的皮层表面引起的心跳和呼吸)。然而, 训练协议 (图 3C-3E) 的最终结果将密切再现现实生活情况26。
如果由两名外科医生执行, 微电极阵列植入的平均手术时间是30分钟以下, 其他人也报告26。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56584/56584fig1.jpg"> 图 1.设置类似于手术室的环境.(A) 头颅 CT 扫描可证实无明显颅内病变。(B) 将头部定位在颅骨钳上。(C) 将头部披上。标本的鼻子在图片的右边, 枕在左边。(D) 切割和倾斜头皮和颞肌肉。<a href="//cloudflare-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/56584/56584fig1large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56584/56584fig2.jpg"> 图 2.露出皮层表面并连接电极基座.(A) 执行大面积的开颅手术。(B) 执行 durotomy。(C) 反射硬脑膜并暴露皮层表面。(D) 将电极基座螺钉钉在开颅边缘附近的颅骨骨上 (插图: 用骨螺钉固定底座的特写)。(E) 用镊子握住脆弱的微电极阵列以避免不需要的接触造成的损坏。<a href="//cloudflare-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/56584/56584fig2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56584/56584fig3.jpg"> 图 3.定位和插入微电极阵列.(A) 弯曲线束以使微电极阵列与皮层表面对齐 (插图: 微电极阵列和皮层的对齐方式的特写)。(B) 将气动冲击器与微电极阵列的背面对准 (插图: 撞击器和微电极阵列对准的特写)。(C) 微电极阵列、线束和电极基座概述。(D) 将 ECOG 网格置于皮层表面上。(E) 靠近电极基座的颈部周围的皮肤。<a href="//cloudflare-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/56584/56584fig3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

Watch this Scientific Journal Video about Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model at JoVE.com

Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model

应用甲醛固定人尸体模型植入皮层微电极阵列的外科训练

我们设计了一个程序, 其中一个甲醛固定的人的尸体是用来协助外科的训练, 将微电极阵列植入人脑的大脑皮层。

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. ...

surgical-training-for-implantation-neocortical-microelectrode-arrays

Universidad San Sebastian

Research

JoVE Journal

Medicine

11.3K 次观看.  Wyss Center for Bio and Neuroengineering, Geneva. 我们设计了一个程序, 其中一个甲醛固定的人的尸体是用来协助外科的训练, 将微电极阵列植入人脑的大脑皮层。

视频: Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

联合穿梭盒子训练与电的Cortex记录和刺激作为一种工具来研究感知和学习

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

科研

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

Large-scale Recording of Neurons by Movable Silicon Probes in Behaving Rodents

A major challenge in neuroscience is linking behavior to the collective activity of neural assemblies. Understanding of input-output relationships of neurons and circuits requires methods with the spatial selectivity and temporal resolution appropriate for mechanistic analysis of neural ensembles in the behaving animal, i.e. recording of representatively large samples of isolated single neurons. Ensemble monitoring of neuronal activity has progressed remarkably in the past decade in both small and large-brained animals, including human subjects1-11. Multiple-site recording with silicon-based devices are particularly effective because of their scalability, small volume and geometric design.
Here, we describe methods for recording multiple single neurons and local field potential in behaving rodents, using commercially available micro-machined silicon probes with custom-made accessory components. There are two basic options for interfacing silicon probes to preamplifiers: printed circuit boards and flexible cables. Probe supplying companies (<a href="http://www.neuronexustech.com/" >http://www.neuronexustech.com/</a>; <a href="http://www.sbmicrosystems.com/">http://www.sbmicrosystems.com/</a>; <a href="http://www.acreo.se/">http://www.acreo.se/</a>) usually provide the bonding service and deliver probes bonded to printed circuit boards or flexible cables. Here, we describe the implantation of a 4-shank, 32-site probe attached to flexible polyimide cable, and mounted on a movable microdrive. Each step of the probe preparation, microdrive construction and surgery is illustrated so that the end user can easily replicate the process.

We describe methods for large-scale recording of multiple single units and local field potential in behaving rodents with silicon probes. Drive fabrication, probe attachment to the drive and probe implantation processes are illustrated in sufficient details for easy replication.

移动硅探针的神经行为鼠害的大型记录

A major challenge in neuroscience is linking behavior to the collective activity of neural assemblies. Understanding of input-output relationships of ...

Intact Histological Characterization of Brain-implanted Microdevices and Surrounding Tissue

Research into the design and utilization of brain-implanted microdevices, such as microelectrode arrays, aims to produce clinically relevant devices that interface chronically with surrounding brain tissue. Tissue surrounding these implants is thought to react to the presence of the devices over time, which includes the formation of an insulating "glial scar" around the devices. However, histological analysis of these tissue changes is typically performed after explanting the device, in a process that can disrupt the morphology of the tissue of interest.
Here we demonstrate a protocol in which cortical-implanted devices are collected intact in surrounding rodent brain tissue. We describe how, once perfused with fixative, brains are removed and sliced in such a way as to avoid explanting devices. We outline fluorescent antibody labeling and optical clearing methods useful for producing an informative, yet thick tissue section. Finally, we demonstrate the mounting and imaging of these tissue sections in order to investigate the biological interface around brain-implanted devices.

Here we present a histological method for capturing, labeling, optically clearing, and imaging the intact brain tissue interface around chronically implanted microdevices in rodent brain tissue. Results from the techniques comprising this method are useful for understanding the impact of various penetrating brain-implants on their surrounding tissue.

脑植入的微型器件及周围组织的完整的组织学特性研究

Research  into the design and utilization of brain-implanted microdevices, such as  microelectrode arrays, aims to produce clinically relevant devices ...

Chronic Implantation of Whole-cortical Electrocorticographic Array in the Common Marmoset

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent development of thin, flexible ECoG electrodes has enabled conduction of stable recordings of large-scale cortical activity. We have developed a whole-cortical ECoG array for the common marmoset. The array continuously covers almost the entire lateral surface of cortical hemisphere, from the occipital pole to the temporal and frontal poles, and it captures whole-cortical neural activity in one shot. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain. Marmosets have two advantages regarding ECoG recordings, one being the homologous organization of anatomical structures in humans and macaques, including frontal, parietal, and temporal complexes. The other advantage is that the marmoset brain is lissencephalic and contains a large number of complexes, which are more difficult to access in macaques with ECoG, that are exposed to the brain surface.These features allow direct access to most cortical areas beneath the surface of the brain. This system provides an opportunity to investigate global cortical information processing with high resolutions at a sub-millisecond order in time and millimeter order in space.

We have developed a whole-cortical electrocorticographic array for the common marmoset that continuously covers almost the entire lateral surface of cortex, from the occipital pole to the temporal and frontal poles. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain.

常见马莫塞的全皮质电皮质阵列的慢性植入

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent ...

Stereotaxic Surgery for Implantation of Microelectrode Arrays in the Common Marmoset (Callithrix jacchus)

Marmosets (Callithrix jacchus) are small non-human primates that are gaining popularity in biomedical and preclinical research, including the neurosciences. Phylogenetically, these animals are much closer to humans than rodents. They also display complex behaviors, including a wide range of vocalizations and social interactions. Here, an effective stereotaxic neurosurgical procedure for implantation of recording electrode arrays in the common marmoset is described. This protocol also details the pre- and postoperative steps of animal care that are required to successfully perform such a surgery. Finally, this protocol shows an example of local field potential and spike activity recordings in a freely behaving marmoset 1 week after the surgical procedure. Overall, this method provides an opportunity to study the brain function in awake and freely behaving marmosets. The same protocol can be readily used by researchers working with other small primates. In addition, it can be easily modified to allow other studies requiring implants, such as stimulating electrodes, microinjections, implantation of optrodes or guide cannulas, or ablation of discrete tissue regions.

Stereotaxic Surgery for Implantation of Microelectrode Arrays in the Common Marmoset Callithrix jacchus

This work presents a protocol to perform a stereotaxic, neurosurgical implantation of&#160;microelectrode arrays in the common marmoset. This method specifically enables electrophysiological recordings in freely behaving animals but can be easily adapted to any other similar neurosurgical intervention in this species (e.g., cannula for drug administration or electrodes for brain stimulation).

在普通马莫塞特中植入微电极阵列的立体外科（Callithrix jacchus）

Marmosets (Callithrix jacchus) are small non-human primates that are gaining popularity in biomedical and preclinical research, including the ...

Preparation and Implantation of Electrodes for Electrically Kindling VGAT-Cre Mice to Generate a Model for Temporal Lobe Epilepsy

It was discovered that electrical kindling of VGAT-Cre mice led to the spontaneous motor and electrographic seizures. A recent paper focused on how unique VGAT-Cre mice were used in developing spontaneous recurring seizures (SRS) after kindling and a likely mechanism - insertion of Cre into the VGAT gene - disrupted its expression and reduced GABAergic tone. The present study extends these observations to a larger cohort of mice, focusing on key issues such as how long the SRS continues after kindling and the effect of the animal's sex and age. This report describes the protocols for the following key steps: making headsets with hippocampal depth electrodes for electrical stimulation and for reading the electroencephalogram; surgery to affix the headset securely on the mouse's skull so that it does not fall off; and key details of the electrical kindling protocol such as duration of the pulse, frequency of train, duration of train, and amount of current injected. The kindling protocol is robust in that it reliably leads to epilepsy in most VGAT-Cre mice, providing a new model to test for novel antiepileptogenic drugs.

This report describes the methods to generate a model of temporal lobe epilepsy based on the electrical kindling of transgenic VGAT-Cre mice. Kindled VGAT-Cre mice may be useful in determining what causes epilepsy and for screening novel therapies.

电点燃VGAT-CRE小鼠电极的制备和植入，以生成颞叶癫痫模型

It was discovered that electrical kindling of VGAT-Cre mice led to the spontaneous motor and electrographic seizures. A recent paper focused on how unique ...

用于小鼠电生理学的经济高效、多功能探针植入系统

The DREAM Implant: A Lightweight, Modular, and Cost-Effective Implant System for Chronic Electrophysiology in Head-Fixed and Freely Behaving Mice

Chronic electrophysiological recordings in rodents have significantly improved our understanding of neuronal dynamics and their behavioral relevance. However, current methods for chronically implanting probes present steep trade-offs between cost, ease of use, size, adaptability, and long-term stability.
This protocol introduces a novel chronic probe implant system for mice called the DREAM (Dynamic, Recoverable, Economical, Adaptable, and Modular), designed to overcome the trade-offs associated with currently available options. The system provides a lightweight, modular and cost-effective solution with standardized hardware elements that can be combined and implanted in straightforward steps and explanted safely for recovery and multiple reuse of probes, significantly reducing experimental costs.
The DREAM implant system integrates three hardware modules: (1) a microdrive that can carry all standard silicon probes, allowing experimenters to adjust recording depth across a travel distance of up to 7 mm; (2) a three-dimensional (3D)-printable, open-source design for a wearable Faraday cage covered in copper mesh for electrical shielding, impact protection, and connector placement, and (3) a miniaturized head-fixation system for improved animal welfare and ease of use. The corresponding surgery protocol was optimized for speed (total duration: 2 h), probe safety, and animal welfare.
The implants had minimal impact on animals&#39; behavioral repertoire, were easily applicable in freely moving and head-fixed contexts, and delivered clearly identifiable spike waveforms and healthy neuronal responses for weeks of post-implant data collection. Infections and other surgery complications were extremely rare.
As such, the DREAM implant system is a versatile, cost-effective solution for chronic electrophysiology in mice, enhancing animal well-being, and enabling more ethologically sound experiments. Its design simplifies experimental procedures across various research needs, increasing accessibility of chronic electrophysiology in rodents to a wide range of research labs.

作者聚焦:通过虚拟现实和动物电生理学了解自然神经元计算

Here, we introduce a lightweight, cost-effective probe implant system for chronic electrophysiology in rodents optimized for ease of use, probe recovery, experimental versatility, and compatibility with behavior.

DREAM 植入物:一种轻便、模块化且经济高效的植入系统，用于头部固定和行为自由的小鼠的慢性电生理学

Chronic electrophysiological recordings in rodents have significantly improved our understanding of neuronal dynamics and their behavioral relevance. ...

应用甲醛固定人尸体模型植入皮层微电极阵列的外科训练

摘要

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此视频中的章节

联合穿梭盒子训练与电的Cortex记录和刺激作为一种工具来研究感知和学习

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

移动硅探针的神经行为鼠害的大型记录

脑植入的微型器件及周围组织的完整的组织学特性研究

常见马莫塞的全皮质电皮质阵列的慢性植入

在普通马莫塞特中植入微电极阵列的立体外科（Callithrix jacchus）

电点燃VGAT-CRE小鼠电极的制备和植入，以生成颞叶癫痫模型

DREAM 植入物:一种轻便、模块化且经济高效的植入系统，用于头部固定和行为自由的小鼠的慢性电生理学

DREAM 植入物:一种轻便、模块化且经济高效的植入系统，用于头部固定和行为自由的小鼠的慢性电生理学

DREAM 植入物:一种轻便、模块化且经济高效的植入系统，用于头部固定和行为自由的小鼠的慢性电生理学