我们感谢丹尼尔·卡尔皮他的帮助下，该项目的早期贡献。我们也感谢她协助艺术品和图像卢西亚·诺沃亚。这项工作是由NIH / NIAID项目资助5P01AI073693-03的支持。

1。四极管制造<ol><li>开始使用绝缘直径12.5微米（0.0005“）的核心铂铱丝从加州精细电线，电线的长度应为目标结构切成适当的长度，例如，至少30厘米长的砍电线针对背下脚海马。 </li><li>在中心折叠线，因此，有两条平行的线，这将是15厘米的长度。悬垂性这根线的中点在一个水平臂，以形成四个平行的导线长度为7.5cm。下一步附加垂褶线的底部附近的橡胶涂层的剪辑，创建的四根电线束。 </li><li>将橡胶剪辑到机动四极管微调，确保导线是绷紧，但不是太紧张或轴承的重量，因为它会破坏在纺纱过程中。 </li><li>四极微调切换到“手动”模式，推操纵杆，“右”，以顺时针方向旋转电线。微调将在约2赫兹旋转，创建一个捆紧的四根导线，以形成四极。 </li><li>应用80顺时针旋转，那么，停止通过推操纵杆上的“向上”。将暂停电动飞旋。接下来，适用于20逆时针旋转（“左”），以释放紧张的四极。最终数目每导线长度的旋转应该是每微米8圈。 </li><li>使用热风枪加热，在下部设置1，400度达到最大值，以熔合线连接在一起，通过熔化的VG粘结涂层。握住热风枪〜2厘米的导线和运行枪向上和向下的直导线长度从几个不同的角度为约5秒。请确保不断扫热枪，而不是持有任何一个位置，因为这将融化并导致HML绝缘电线融合在一起包内。 </li><li>在四极管的顶部附近的水平臂作一个切口，然后释放的四极管在底部从剪辑。剪切的单回路，以便有四极管的一端上的四条独立的导线，这些导线将被电连接到金标签或在后面的步骤中的一电路板。 </li><li>将完成四极，无粉尘控股箱存储，直到驱动器已经完成。 </li></ol> 2。自定义微型硬盘大会<ol><li>首先构建的基础，将保持在Microdrive（S）。植入的微型硬盘（Microdrive）的基础，一般是最稳定的，如果它是在保护和头骨中线沿。本协议描述的步骤，建立一个基地，一个单一的微型硬盘（Microdrive）举行四次聚酰胺管携带者。可以很容易地根据需要添加额外的微型硬盘和管。 </li><li>约20mm见方的一块有机玻璃压克力（5毫米厚）和砂的丙烯酸系成一字形，将让鼠标自由移动，与该驱动器后，它被植入的头开始。 </li><li>接下来，组装驱动单元。使用定制30.3 X 6.3毫米黄铜指南，将携带的传动螺杆。首先，锡黄铜导游一起垂直。垂直的黄铜指南将持有的驱动螺杆和电极，而水平件将被粘到丙烯酸类碱。 </li><li>经过焊接黄铜拼在一起，开始组装驱动器本身通过一个圆头铜螺丝，通过顶部的引导和成聚甲醛塑料块。被设计成使得所述螺纹孔是稍微偏离中心（0.2毫米），在一个面上的非常轻微突起从导向块的方块。这是一面附有电极的聚酰胺管会坐下。 </li><li>聚甲醛块里面指导，螺丝，一路过关斩将，一个线程六角螺母铜螺母，直到几乎触底的引导。不要完全拧紧螺母，而是融化少量的焊锡到年底才能加入螺母和螺钉，但小心不要焊接anyt的兴的指南。现在，旋转的螺丝应该移动的的聚甲醛块向上（顺时针方向）和向下（逆时针）沿螺纹垂直。切断突出过去的焊接螺母的螺纹。 </li><li>一旦驱动器已组装完毕，回去丙烯酸基地，切3毫米宽的槽，将电极驱动。通过插槽，然后使用cryanoacrylate胶，一块固定基地，通过水平黄铜指南。 </li><li>将丙烯酸基在台钳固定到位。底座的顶部放置一个电子接口板（EIB）和两个螺丝孔的位置的标记。 EIBS是提供一个信号的电极布线之间的连接和一个前置放大器探头的微芯片。使用1.5毫米的尖钻头，仔细钻孔螺丝基地上，将举行EIB的痕迹。将欧洲投资银行和线程两个黄铜螺丝插入孔中。 </li><li>使用微解剖剪刀剪四个7毫米长的小段polyamIDE管。线路彼此相邻的四个管折叠实验室磁带上的一块。应用瞬干胶中心一起加入他们的行列，但要小心，不要让胶水管内的自己。允许加入管完全干燥。 </li><li>旋转驱动器基座90度，使，EIB芯片垂直和驱动突出的Delrin块朝上水平放置。通过解剖显微镜下，仔细寻找民建联少量的聚甲醛的脸瞬干胶，上胶，然后将四个连接管。让胶水完全移动驱动器，然后再尝试设置。 </li><li>测试，聚酰胺管牢固地连接，整个组装移动平稳，无触摸的指南或满足任何抵抗。 </li><li>接下来，准备接地螺钉和连接地线的EIB。接地螺钉的，这应该是由黄铜螺钉（3/32“）和打磨下来的只有1-2个线程的线程，直到保持〜1毫米，此螺钉将坐在颅骨内，但不适合渗入脑组织。 </li><li>切一门30毫米的铜导线的长度（确切的长度将取决于头骨上放置动物地面）。铜线的应该是100 - 500μM（0.004-0.02英寸）的直径，这大致相当于38 AWG至24 AWG电线。应用焊剂铜线两端，在一端上，焊料的接地螺丝线的另一端​​，焊接EIB金脚。地线可以预留连接到EIB在植入手术后。 </li><li>接下来的步骤是通过在聚酰胺管引导电极，并把它们连接到的EIB芯片上的通道孔。打开驱动器的螺丝完全顺时针管在其顶部位置。 </li><li>单电极，切一个的50μMStableohm电线50毫米的长度，并引导它通过一种聚酰胺管，允许其延伸至少2.0毫米的管端（针对下托或过去海马）。取一小颗的腈基丙烯酸酯在管的顶部，电线固定管和防止任何导线运动。接下来，连接线一个的EIB通道孔金销的自由端。细剪刀剪掉多余的导线。重复其他微电极。 </li><li>连接四极管，完成四极出的储物盒。引导通过一种聚酰胺管的稠合的四极，并允许它以延长过去的管端（下托或海马）至少为2.0毫米。取一小颗的腈基丙烯酸酯在管的顶部，固定的四极管，并防止任何运动。以四四极管的另一端，松散的电线，每根导线连接到一个的EIB通道孔金销。剪掉多余的导线。重复其他四极管。 </li></ol> 3。 VERSADRIVE大会<ol><li>开始建设四极管VersaDrive;这包括基地，圈地，和帽PIEC的ES。 </li><li>一种聚酰胺管切至10毫米，并引导它通过最小的孔四极管载体上。允许管延伸过去的载体非常轻微（0.5毫米）。使用5分钟环氧胶聚酰胺管，小心不要让环氧进入管本身。重复其他三个管和运营商。 </li><li>环氧树脂后已完全设置，引导每个聚酰胺管通过的四个孔上VERSADRIVE基地之一。一旦所有四个管是通过他们的孔，通过外孔昆虫针推，将举行四极承运人铁路为载体，以旅游线路和服务。其他三个运营商重复。 </li><li>一顶帽子排队四个昆虫针帽涵盖基地和四极携带者所在的上限范围内。主题1毫米x 5毫米机螺丝帽和通过适当的孔进入四极管载体。这将是驱动螺杆，用于向上和向下移动的载流子。精华吃这其他三个螺丝。 </li><li>将所有螺丝顺时针旋转，直到四极的运营商都在他们的首要位置，并通过帽开口可见聚酰胺管。使用细微解剖剪刀，切断油管正下方（1毫米）的基础，使所有四个的聚酰胺管是相同长度的。 </li><li>使用解剖显微镜，仔细一极管穿线通过聚酰胺管。重要的是要保持四极线笔直的，因为它的进步通过管任何扭结或弯曲使它很难完全线程通过四极管。重复其他三个四极管。 </li><li>一旦所有的四极管是在管，慎重适用氰基丙烯酸酯每管顶部的一小滴，确保各自管内的四极管。请小心不要让任何瞬干胶运营商之间的或松散的四极线帽突出。 </li><li>切四极管，所以他们只延伸过去的管2.0毫米（下脚海马）。然后将驱动器基座（四个昆虫针插入）到VERSADRIVE夹具。的夹具的另一半将举行VersaDrive的上限，具有用于使信道连接的所有的插座孔。 </li><li>打开驱动器的螺丝逆时针完全如此，四极管是在他们的最低位置。 </li><li>黄金插座连接的四极线之前，首先连接接地线连接到帽​​。 VERSADRIVE帽有两个销孔的两排孔的中心位置处的接地连接。削减至少30毫米的铜线（取决于在头骨上放置地面），并引导它通过一个中心孔。在铜导线应为100 - 500μM（0.004-0.02英寸）的直径，这大致相当于38 AWG至24 AWG电线。通过孔金贮器推到位赶上铜线，修剪任何多余的电线。铜线的另一端​​，将助焊剂和soldeR此​​线端的接地螺钉（见2.11）。重复第二地线。 </li><li>接下来，引导全体通过各自的插座孔帽上的松散的四极线（应该有16个）。这是最好的开始一个四极管并拧到相应的四个孔，最终将直接在它上面的每根电线。个人四极导线应压光处理，因为他们是脆弱的，可以很容易卷曲，如果用力心惊肉跳。排着队昆虫针孔和安装帽按拟合基地。 </li><li>四极管电线突出的上限，按适合的黄金容器捕捉到位，四极线进行电气连接。大约50％的导线将被裁剪（上面的帽），一旦金插座被向下推。修剪任何多余的线从顶部帽仍然突出。在极少数情况下（小于5％），向下推黄金插座将粉碎丝并打破它下面的插座，导致断开连接通道。这断线可能无法实现，直到阻抗测试和电镀步骤（见4.7）。 </li><li>重复其他三个四极管的压入过程。打开驱动器的螺丝顺时针它们移回顶部，并确保该驱动器的运动是光滑的。 </li></ol> 4。镀金电极提示<ol><li>无论是什么类型所使用的微电极，在电极的前端应该是镀金的，为了减少尖端阻抗。这将最大限度地可靠地记录和歧视单机动作电位的能力。测试电极阻抗使用Neuralynx nanoZ设备。的nanoZ是一个基于计算机的的移动设备，其测量阻抗，允许自动电镀。 </li><li>首先将微硬盘螺丝（逆时针）来的最低位置。然后牢固地安装在夹具上的微型硬盘（Microdrive），将允许降低到镀金溶液中的电极尖端。 </li><li>填充聚甲醛树脂塔SIFCO金溶液和其他塔用蒸馏水。降低电极尖端到金溶液。 </li><li>插头nanoZ的USB电缆连接到基于Windows的计算机，然后打开的nanoZ程序。这项计划将给予阻抗读数和执行镀金，每个连接通道的微型硬盘（Microdrive）。 </li><li>转到设备“下拉列表，并选择nanoZ后，它会显示”已建立连接“窗口底部的。接下来，测试在下拉菜单中选择相应的适配器。点击“测试阻抗”，并设置检测频率为1004赫兹（40周期，暂停0毫秒）。点击“测试探针”，这将打开“探头报告”窗口，显示所有可用的渠道与他们MΩ读数。保存这些阻抗值，然后点击磁盘图标，或选择“文件”“保存报告”。 </li><li>接下来，点击“直流电镀”，并指派下面的值：模式=匹配阻抗，电镀电流=μA，-1.0目标= 350kΩ的在1004 Hz，5次试验，5秒时间间隔，2秒暂停。 </li><li>点击“自动铸”。程序将首先读出每个通道的阻抗，然后应用到该通道指定的电流，重新测试的阻抗和应用，直到达到目标阻抗（或一个较低的值）作为当前需要。虽然我们的目标是降低电极的阻抗，这是可能的，通道将电镀下面的100kΩ的值。在这种情况下，它可能是四极管上的相邻的电线已被短接在一起。如果发生这种情况，反向电流极性（+ 1.0ĩA）去除多余的金颗粒，重新测试该通道的阻抗，然后重复电镀。典型的最后一捆四个12.5微米线的阻抗值的范围从150 - 325kΩ的。 </li><li>如果有任何的单信道，并没有镀低于350kΩ，重复电镀过程。该计划将跳过渠道已经达到了目标，并只会板的渠道都没有。 </li><li>一旦所有通道都被镀到一个可接受的阻抗，关闭nanoZ的程序和断开设备连接。提高电极的电镀溶液，以冲洗掉多余的金颗粒，降低到蒸馏水中的聚甲醛树脂塔的提示。 </li><li>打开驱动器螺丝顺时针旋转，直到电极提高他们的榜首位置。现在的微型硬盘（Microdrive）和电极植入准备。 </li></ol>

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L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamics+of+the+hippocampal+ensemble+code+for+space.">Dynamics of the hippocampal ensemble code for space.</a> Science. 261 (5124), 1055-1058 (1993).</li><li>Buzs&#225;ki, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Rhythms of the Brain. , (2006).</li><li>McHugh, T. J., Blum, K. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+hippocampal+representation+of+space+in+CA1-specific+NMDAR1+knockout+mice.">Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout mice.</a> Cell. 87 (7), 1339-1349 (1996).</li><li>Resnik, E., McFarland, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+GluA1+deletion+on+the+hippocampal+population+code+for+position.">The effects of GluA1 deletion on the hippocampal population code for position.</a> J. Neurosci. 32 (26), 8952-8968 (2012).</li><li>Cacucci, F., Yi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Place+cell+firing+correlates+with+memory+deficits+and+amyloid+plaque+burden+in+Tg2576+Alzheimer+mouse+model.">Place cell firing correlates with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model.</a> Proc. Natl. Acad. Sci. U.S.A. 105 (22), 7863-7868 (2008).</li><li>Sigurdsson, T., Stark, K. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+hippocampal-prefrontal+synchrony+in+a+genetic+mouse+model+of+schizophrenia.">Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia.</a> Nature. 464 (7289), 763-767 (2010).</li><li>Engel, A. K., Moll, C. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Invasive+recordings+from+the+human+brain:+clinical+insights+and+beyond.">Invasive recordings from the human brain: clinical insights and beyond.</a> Nat. Rev. Neurosci. 6 (1), 35-47 (2005).</li><li>Cash, S. S., Halgren, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+human+K-complex+represents+an+isolated+cortical+down-state.">The human K-complex represents an isolated cortical down-state.</a> Science. 324 (5930), 1084-1087 (2009).</li></ol>

作者宣称，他们有没有竞争经济利益。

我们已经描述了一组技术构建细胞外单位记录和字段的潜在活性在小鼠的轻量，小型的微型硬盘。构建自定义的微型硬盘，老式的丙烯酸玻璃（甲基丙烯酸甲酯）的基地，核心系统可以很容易地适应多个驱动器和针对广泛的神经区域。我们已经成功地修改了系统记录从多个脑目标和较大的阵列小鼠录音。随着进一步的修改，电动驱动元件可以结合，以便能够远程，可能更精确，电极放置7。</su...

利用微电极技术记录外体内的神经信号在神经科学1，2有一个长期和价值的传统。许多自由活动动物的脑区能够记录电活动，但是，最近的技术，正在成为越来越普遍变得更加复杂和用户友好的软件包的神经信号的采集，分析和歧视， 4。在软件方面的技术进步也伴随着可植入设备的重量和体积减少，已充分缩减小型哺乳动物，如小鼠的记录。通过使用轻量级的组件（主要是塑料），研究人员能够构建微型硬盘，使电极或四极管，以针对各种各样的大脑区域5-7的独立定位。即使是脑深部结构，如杏仁核和纹状体5，可以经常有针对性的选择适当长的传动螺杆。这些记录技术使研究人员能够获得高保真神经信号，并注册单个神经元的电活动记录细胞内8，9。使用这些类型的微型硬盘，我们已经成功地记录单台长达两个月的小鼠植入后10。此外，设备的轻量的特性（约1.5〜2.0克）导致的行为表现，是许多行为的任务中的非注入小鼠比较。特别是，我们已经证明，植入小鼠表现出正常的表现在新物体识别任务10和对象的地方任务（未公布数据）。 使用微型硬盘连接到多个四极管，使研究人员能够监测和分析在网络层面的神经活动同时也记录从大脑内的多个单个单元。记录这些四极管单位的身份证明文件的目的有几大优势，并让多个单单元11高精度采集和歧视。我们描述了如何制造和镏金四极束，随后将它们加载到驾驶电极载体。一种类型的驱动器托架，我们描述的是市售的，另一种是简单，但很容易地扩展，驱动设计，可容纳多个运营商和四极管安排没有重大投资资源。

<table border="1">
		<tbody>
		 <tr>
			<td>Name of Reagent/Material</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		 </tr>
		 <tr>
			<td>0.0005" (12.5 &mu;M) diameter Platinum-Iridium wire </td>
			<td>California Fine Wire</td>
			<td>CFW#100-167</td>
			<td>HML VG insulated <a href="http://www.calfinewire.com" target="_blank">www.calfinewire.com</a></td>
		 </tr>
		 <tr>
			<td>0.002" (50 &mu;M) diameter Stableohm 675 wire</td>
			<td>California Fine Wire</td>
			<td>CFW# 100-188</td>
			<td>HML insulated Ni-Cr</td>
		 </tr>
		 <tr>
			<td>polyamide tubing</td>
			<td>Polymicro Technologies</td>
			<td>1068150020</td>
			<td>99 micron I.D., 166 micron O.D. <a href="http://www.polymicro.com" target="_blank">www.polymicro.com</a></td>
		 </tr>
		 <tr>
			<td>brass guides</td>
			<td>World Plastics Inc</td>
			<td></td>
			<td>3.3 x 6.6 mm</td>
		 </tr>
		 <tr>
			<td>Delrin blocks</td>
			<td>World Plastics Inc</td>
			<td></td>
			<td>3.13 x 2.5 mm</td>
		 </tr>
		 <tr>
			<td>Fillister head brass screws</td>
			<td>J.I. Morris Co.</td>
			<td>00-90 x 1/2</td>
			<td>drive screw <a href="http://www.jimorrisco.com" target="_blank">www.jimorrisco.com</a></td>
		 </tr>
		 <tr>
			<td>hex brass nuts</td>
			<td>J.I. Morris Co.</td>
			<td>00-90</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Fillister head brass screws</td>
			<td>J.I. Morris Co.</td>
			<td>000-120 x 3/32</td>
			<td>EIB mount and ground screw</td>
		 </tr>
		 <tr>
			<td>plexiglass acrylic</td>
			<td>Canal Street Plastics</td>
			<td></td>
			<td>5 mm thick, clear, <a href="http://www.cpcnyc.com" target="_blank"> www.cpcnyc.com</a></td>
		 </tr>
		 <tr>
			<td>cyanoacrylate</td>
			<td>Krazy Glue</td>
			<td></td>
			<td>2 g tube</td>
		 </tr>
		 <tr>
			<td>electronic interface board</td>
			<td>Neuralynx</td>
			<td>EIB-18</td>
			<td><a href="http://www.neuralynx.com" target="_blank">www.neuralynx.com</a></td>
		 </tr>
		 <tr>
			<td>non-cyanide gold solution</td>
			<td>SIFCO</td>
			<td>SIFCO 5355</td>
			<td><a href="http://www.sifcoasc.com" target="_blank">www.sifcoasc.com</a></td>
		 </tr>
		 <tr>
			<td>VersaDrive 4</td>
			<td>Neuralynx</td>
			<td></td>
			<td>four tetrode model</td>
		 </tr>
		 <tr>
			<td>tetrode assembly station</td>
			<td>Neuralynx</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>motorized tetrode spinner</td>
			<td>Neuralynx</td>
			<td>tetrode spinner 2.0</td>
			<td></td>
		 </tr>
		 <tr>
			<td>VersaDrive jig</td>
			<td>Neuralynx </td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>soldering iron</td>
			<td>Radio Shack </td>
			<td>64-2802B</td>
			<td><a href="http://www.radioshack.com" target="_blank">www.radioshack.com</a></td>
		 </tr>
		 <tr>
			<td>nanoZ</td>
			<td>Neuralynx</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>small bit drill/driver</td>
			<td>Ram Products </td>
			<td>Rampower 35</td>
			<td>with footpedal controller, <a href="http://www.ramprodinc.com" target="_blank">www.ramprodinc.com</a></td>
		 </tr>
		 <tr>
			<td>drill bits</td>
			<td>Small Parts, Inc.</td>
			<td></td>
			<td>3/32" bits, <a href="http://www.smallpartsinc.com" target="_blank">www.smallpartsinc.com</a></td>
		 </tr>
		 <tr>
			<td>dissecting microscope</td>
			<td>Olympus </td>
			<td>SZ-60</td>
			<td><a href="http://www.olympusamerica.com" target="_blank">www.olympusamerica.com</a></td>
		 </tr>
		 <tr>
			<td>heat gun</td>
			<td>Alphawire</td>
			<td>Fit gun 3</td>
			<td>use setting "1" only, <a href="http://www.alphawire.com" target="_blank">www.alphawire.com</a></td>
		 </tr>
		 <tr>
			<td>26 AWG copper wire</td>
			<td>Arcor Electronics</td>
			<td>F26</td>
			<td>for ground wires, <a href="http://www.arcorelectronics.com" target="_blank"> www.arcorelectronics.com</a></td>
		 </tr>
		 <tr>
			<td>soldering flux</td>
			<td>Eagle</td>
			<td>2 oz, #205</td>
			<td></td>
		 </tr>
		 <tr>
			<td>0.02" diameter solder</td>
			<td>Kester</td>
			<td>24-6337-0010</td>
			<td><a href="http://www.kester.com" target="_blank"> www.kester.com</a></td>
		 </tr>
		 <tr>
			<td>benchtop vise</td>
			<td>Vacu-Vise</td>
			<td>Model 300</td>
			<td></td>
		 </tr>
		 <tr>
			<td>fiber optic light</td>
			<td>Nikon </td>
			<td>MKII</td>
			<td>dual light arms, <a href="http://www.nikon.com" target="_blank"> www.nikon.com</a></td>
		 </tr>
		 <tr>
			<td>5-min epoxy</td>
			<td>Allied Electronics</td>
			<td></td>
			<td>25 ml, <a href="http://www.alliedelec.com" target="_blank"> www.alliedelec.com</a></td>
		 </tr>
		 <tr>
			<td>fine tweezers</td>
			<td>Roboz Surgical Instrument Co.</td>
			<td>RS-4907, RS-5010</td>
			<td>INOX material, <a href="http://www.roboz.com" target="_blank"> www.roboz.com</a></td>
		 </tr>
		 <tr>
			<td>micro dissecting scissors</td>
			<td>Roboz Surgical Instrument Co.</td>
			<td>RS-5880</td>
			<td></td>
		 </tr>
		</tbody>
 </table>
 Table 1. Materials and reagents used for constructing tetrodes and microdrives.

construction of microdrive arrays for chronic neural recordings in awake behaving mice

国家最先进的电生理记录自由活动动物的大脑，使研究人员能够同时检测局部场电位（的LFP）从单个细胞的神经元和动作电位的人群，从事动物实验相关的任务。长期植入微型硬盘让大脑录音持续了几个星期期间。小型化的驱动器和轻量级组件，让这些长期的记录发生在小型哺乳动物，如小鼠。通过使用四极管，它包括四个电极，其中每根导线有一个直径为12.5微米的紧密编织束，它是可以分离生理活性的神经元在浅表的大脑区域，如大脑皮层，背侧海马和下托，以及更深的区域，如纹状体和杏仁核。此外，这种技术确保稳定，高保真神经的录音作为动物的挑战与多款TY行为的任务。这手稿描述几种技术进行了优化，从小鼠大脑记录。首先，我们展示了如何制造四极管，将它们加载到驾驶管，板金他们的技巧，以降低其阻抗MΩkΩ范围。其次，我们将展示如何构建一个定制的微型硬盘（Microdrive）组件，携带和移动的四极管垂直，使用廉价的材料。第三，我们显示的步骤组装市售的微型硬盘（Neuralynx VERSADRIVE），旨在进行独立移动四极管。最后，我们提出了局部场电位和单机信号在小鼠背下脚获得的典型结果。这些技术可以很容易地修改以适应不同类型的电极阵列和对小鼠脑组织的记录方案。

<p class="jove_content"后植入的微驱动器和降低电极的大脑预定目标，一个放大的数据采集系统，如一个Neuralynx山猫-8，需要用于记录神经信号。代表神经的局部场电位的录音（局部区域电位）和示于单一单位动作电位（通常被​​称为“尖峰”）从小鼠背侧下托<strong&gt;图2</strong&gt;。 LFP信号采样3 kHz和0.1-500赫兹之间的带通滤波（<strong&gt;图2A</strong&gt;和<strong&gt; 2B</strong&gt;）。<strong&gt;图2A</strong&gt;显示四个连续采样LFP?...

Watch this Scientific Journal Video about Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice at JoVE.com

Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

在体内的电生理记录从小鼠的脑信号的设计和组装的微型硬盘进行说明。通过将微电极束驾驶坚固的运营商，这些技术允许长期和稳定的神经录音。轻巧的设计可以不受限制以下驱动器植入动物的行为表现。

清醒的行为小鼠慢性神经录音的微型硬盘阵列建设

State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field ...

construction-microdrive-arrays-for-chronic-neural-recordings-awake

Research

JoVE Journal

Behavior

20.0K 次观看.  North Shore LIJ Health System. 在体内的电生理记录从小鼠的脑信号的设计和组装的微型硬盘进行说明。通过将微电极束驾驶坚固的运营商，这些技术允许长期和稳定的神经录音。轻巧的设计可以不受限制以下驱动器植入动物的行为表现。

视频: Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving 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

Automated, Quantitative Cognitive/Behavioral Screening of Mice: For Genetics, Pharmacology, Animal Cognition and Undergraduate Instruction

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the &#34;cloud&#34; and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in&#160;cabinet; two such cabinets (16 environments) may be controlled by one computer.

Fully automated system for measuring physiologically meaningful properties of the mechanisms mediating spatial localization, temporal localization, duration, rate&#160;and probability estimation, risk assessment, impulsivity, and the accuracy and precision of memory, in order to assess the effects of genetic and pharmacological manipulations on foundational mechanisms of cognition in mice.

小鼠自动化，定量认知/行为筛选：对于遗传学，药理学，动物认知与本科教学

We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and ...

Cortical Source Analysis of High-Density EEG Recordings in Children

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2, because the composition and spatial configuration of head tissues changes dramatically over development3.&#160;
In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how&#160;EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.&#160;

In recent years, there has been increasing interest in estimating the cortical sources of scalp measured electrical activity for cognitive neuroscience experiments. This article describes how high density EEG is acquired and how recordings are processed for cortical source estimation in children from the age of 2 years at the London Baby Lab.

高密度的脑电图记录在儿童的皮质来源分析

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and ...

A Novel Experimental and Analytical Approach to the Multimodal Neural Decoding of Intent During Social Interaction in Freely-behaving Human Infants

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental paradigms and analysis tools have been limited to constrained laboratory tasks and contexts due to technical limitations imposed by the available set of measuring and analysis techniques and the age of the subjects. These limitations severely limit the study of developmental neural dynamics and associated neural networks engaged in cognition, perception and action in infants performing &#8220;in action and in context&#8221;. This protocol presents a novel approach to study infants and young children as they freely organize their own behavior, and its consequences in a complex, partly unpredictable and highly dynamic environment. The proposed methodology integrates synchronized high-density active scalp electroencephalography (EEG), inertial measurement units (IMUs), video recording and behavioral analysis to capture brain activity and movement non-invasively in freely-behaving infants. This setup allows for the study of neural network dynamics in the developing brain, in action and context, as these networks are recruited during goal-oriented, exploration and social interaction tasks.

This protocol presents a novel methodology for the neural decoding of intent from freely-behaving infants during unscripted social interaction with an actor. Neural activity is acquired using non-invasive high-density active scalp electroencephalography (EEG). Kinematic data is collected with inertial measurement units and supplemented with synchronized video recording.

在自由，表现人类婴儿一种新的实验和分析方法意向的多模态神经解码期间社会互动

Understanding typical and atypical development remains one of the fundamental questions in developmental human neuroscience. Traditionally, experimental ...

A Pressure Injection System for Investigating the Neuropharmacology of Information Processing in Awake Behaving Macaque Monkey Cortex

The top-down modulation of feed-forward cortical information processing is functionally important for many cognitive processes, including the modulation of sensory information processing by attention. However, little is known about which neurotransmitter systems are involved in such modulations. A practical way to address this question is to combine single-cell recording with local and temporary neuropharmacological manipulation in a suitable animal model. Here we demonstrate a technique combining acute single-cell recordings with the injection of neuropharmacological agents in the direct vicinity of the recording electrode. The video shows the preparation of the pressure injection/recording system, including preparation of the substance to be injected. We show a rhesus monkey performing a visual attention task and the procedure of single-unit recording with block-wise pharmacological manipulations.

Here, we show the pressure injection of neuropharmacological substances during single-cell recording in an awake, behaving macaque monkey. This procedure allows pharmacological manipulation in the direct vicinity of a cortical recording site.

对调查信息处理的神经药理学清醒行为猕猴皮质压力喷射系统

The top-down modulation of feed-forward cortical information processing is functionally important for many cognitive processes, including the modulation ...

Using Laser Doppler Imaging and Monitoring to Analyze Spinal Cord Microcirculation in Rat

Laser Doppler flowmetry (LDF) is a noninvasive method for blood flow (BF) measurement, which makes it preferable for measuring microcirculatory alterations of the spinal cord. In this article, our goal was to use both Laser Doppler imaging and monitoring to analyze the change of BF after spinal cord injury. Both the laser Doppler image scanner and the probe/monitor were being employed to obtain each readout. The data of LDPI provided a local distribution of BF, which gave an overview of perfusion around the injury site and made it accessible for comparative analysis of BF among different locations. By intensely measuring the probing area over a period of time, a combined probe was used to simultaneously measure the BF and oxygen saturation of the spinal cord, showing overall spinal cord perfusion and oxygen supply. LDF itself has a few limitations, such as relative flux, sensitivity to movement, and biological zero signal. However, the technology has been applied in clinical and experimental study due to its simple setup and rapid measurement of BF.

Here we present a combination of laser Doppler perfusion imaging (LDPI) and laser Doppler perfusion monitoring (LDPM) to measure spinal cord local blood flows and oxygen saturation (SO2), as well as a standardized procedure for introducing spinal cord trauma on rat.

激光多普勒成像与监测在大鼠脊髓微循环分析中的应用

Laser Doppler flowmetry (LDF) is a noninvasive method for blood flow (BF) measurement, which makes it preferable for measuring microcirculatory ...

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 ...

A Behavioral Assay for Investigating the Role of Spatial Memory During Instinctive Defense in Mice

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often stereotyped actions elicited in response to innately aversive sensory stimuli, but their success requires enough flexibility for adapting to different spatial environments, which can change rapidly. Here, we describe a behavioral assay to evaluate the influence of learned spatial knowledge on defensive behaviors in mice. We have adapted the widely used Barnes maze spatial memory assay to investigate how mice navigate to a shelter during escape responses to innately aversive sensory stimuli in a novel environment, and how they adapt to acute changes in the environment. This new assay is an ethological paradigm that does not require training and exploits the natural exploration patterns and navigation strategies in mice. We propose that the set of protocols described here are a powerful means of studying goal-directed behaviors and stimulus-triggered navigation, which should be of interest to both the fields of instinctive behaviors and spatial memory.

This protocol describes a behavioral assay, based on the Barnes maze test, to study how instinctive defensive actions are modified by the knowledge of spatial environment.

一种研究空间记忆在小鼠本能防御中作用的行为分析法

Evolution has selected a repertoire of defensive behaviors that are essential for survival across all animal species. These behaviors are often ...

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by many patients prompts the need to develop new therapeutic alternatives and to better understand the etiology of the disorder. Pre-clinical models with translational merits are rudimentary for this task. Here we present a protocol for the unpredictable chronic mild stress (UCMS) method in mice. In this protocol, adolescent mice are chronically exposed to interchanging unpredictable mild stressors. Resembling the pathogenesis of depression in humans, stress exposure during the sensitive period of mice adolescence instigates a depressive-like phenotype evident in adulthood. UCMS can be used for screenings of antidepressants on the variety of depressive-like behaviors and neuromolecular indices. Among the more prominent tests to assess depressive-like behavior in rodents is the sucrose preference test (SPT), which reflects anhedonia (core symptom of depression). The SPT will also be presented in this protocol. The ability of UCMS to induce anhedonia, instigate long-term behavioral deficits and enable reversal of these deficits via chronic (but not acute) treatment with antidepressants strengthens the protocol&#39;s validity compared to other animal protocols for inducing depressive-like behaviors.

Here we present the unpredictable chronic mild stress protocol in mice. This protocol induces a long-term depressive-like phenotype and enables to assess the efficacy of putative antidepressants in reversing the behavioral and neuromolecular depressive-like deficits.

诱导小鼠快感缺失的不可预测慢性轻度应力协议

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by ...

Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget

Ethologically relevant behavioral testing is a critical component of any study that uses mouse models to study the cognitive effects of various physiological or pathological changes. The object location task (OLT) and the novel object recognition task (NORT) are two effective behavioral tasks commonly used to reveal the function and relative health of specific brain regions involved in memory. While both of these tests exploit the inherent preference of mice for the novelty to reveal memory for previously encountered objects, the OLT primarily evaluates spatial learning, which relies heavily on hippocampal activity. The NORT, in contrast, evaluates non-spatial learning of object identity, which relies on multiple brain regions. Both tasks require an open-field-testing arena, objects with equivalent intrinsic value to mice, appropriate environmental cues, and video recording equipment and the software. Commercially available systems, while convenient, can be costly. This manuscript details a simple, cost-effective method for building the arenas and setting up the equipment necessary to perform the OLT and NORT. Furthermore, the manuscript describes an efficient testing protocol that incorporates both OLT and NORT and provides typical methods for data acquisition and analysis, as well as representative results. Successful completion of these tests can provide valuable insight into the memory function of various mouse model systems and appraise the underlying neural regions that support these functions.

Here we provide a protocol which includes comprehensive instructions for the economical establishment of murine object location and novel object recognition behavioral testing, including the design, cost, and construction of required equipment as well as execution of behavioral testing, data collection, and analysis.