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Fully integrated silicon probes for high-density recording of neural activity

机译:完全集成的硅探针,用于高密度记录神经活动

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摘要

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures(1,2). Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging(3-5) offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal-oxide-semiconductor (CMOS) processing-compatible low-impedance TiN6 sites that tile a single 10-mm long, 70 x 20-mu m cross-section shank. The 6 x 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.
机译:感觉,运动和认知操作涉及浅表和深层结构中跨多个大脑区域的大型神经元群体的协同作用(1,2)。现有的细胞外探针以极好的空间和时间(亚毫秒)分辨率记录神经活动,但每柄只有几十个神经元。光学Ca2 +成像(3-5)提供了更多的覆盖范围,但缺乏可靠地区分单个尖峰所需的时间分辨率,并且无法测量局部场电势。迄今为止,尚无与在不受限制的动物中使用兼容的技术将高时空分辨率与大体积覆盖结合在一起。在这里,我们设计,制造和测试了一种新型的称为Neuropixels的硅探针,可以满足这一需求。每个探针具有384个记录通道,这些通道可通过可编程方式寻址960个互补的金属氧化物半导体(CMOS)处理兼容的低阻抗TiN6部位,这些部位铺装了一个10mm长,70 x20μm的横截面柄。 6 x 9 mm的探头底座是用柄在单个芯片上制造的。电压信号在基础上经过滤波,放大,多路复用和数字化处理,从而可以直接传输来自探头的无噪声数字数据。密集的记录位点和高通道数相结合,从植入在小鼠和大鼠中的每个探针的数百个神经元中产生了良好隔离的加标活性。使用两个探针,从一个清醒的小鼠的五个脑结构中同时记录了700多个完全隔离的单个神经元。 Neuropixels探针的完全集成的功能和较小的尺寸允许在自由移动的动物中记录来自几个大脑结构的大量神经元。高性能电极技术和可扩展芯片制造方法的结合为记录行为期间大脑范围的神经活动开辟了一条道路。

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  • 来源
    《Nature》 |2017年第7679期|232-236|共5页
  • 作者单位

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    UCL, Inst Neurol, London WC1N 3BG, England|UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6DE, England|UCL, Inst Ophthalmol, London EC1V 9EL, England;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA;

    UCL, Dept Cell & Dev Biol, London WC1E 6BT, England|UCL, Sainsbury Wellcome Ctr, London W1T 4JG, England;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA|Univ British Columbia, Dept Neurol, Vancouver, BC V6T 2B5, Canada;

    IMEC, Kapeldreef 75, B-3001 Heverlee, Leuven, Belgium;

    Neuroelect Res Flanders, Kapeldreef 75, B-3001 Leuven, Belgium|Katholieke Univ Leuven, Dept Biol, Naamsestr 59, B-3001 Leuven, Belgium;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA|White Matter LLC, 999 3rd Ave 700, Seattle, WA 98104 USA;

    IMEC, Kapeldreef 75, B-3001 Heverlee, Leuven, Belgium|Neuroelect Res Flanders, Kapeldreef 75, B-3001 Leuven, Belgium|Katholieke Univ Leuven, Dept Biol, Naamsestr 59, B-3001 Leuven, Belgium|VIB, B-3001 Leuven, Belgium;

    Neuroelect Res Flanders, Kapeldreef 75, B-3001 Leuven, Belgium;

    IMEC, Kapeldreef 75, B-3001 Heverlee, Leuven, Belgium;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6DE, England|UCL, Wolfson Inst Biomed Res, Gower St, London WC1E 6BT, England;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA;

    IMEC, Kapeldreef 75, B-3001 Heverlee, Leuven, Belgium;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA|Univ British Columbia, Dept Neurol, Vancouver, BC V6T 2B5, Canada;

    IMEC, Kapeldreef 75, B-3001 Heverlee, Leuven, Belgium;

    UCL, Inst Neurol, London WC1N 3BG, England|UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6DE, England|Univ Leicester, Ctr Syst Neurosci, Leicester LE1 7QR, Leics, England;

    UCL, Inst Neurol, London WC1N 3BG, England;

    IMEC, Kapeldreef 75, B-3001 Heverlee, Leuven, Belgium;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    UCL, Inst Neurol, London WC1N 3BG, England|UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6DE, England;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

    UCL, Inst Ophthalmol, London EC1V 9EL, England;

    UCL, Inst Neurol, London WC1N 3BG, England|UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6DE, England;

    Allen Inst Brain Sci, 615 Westlake Ave North, Seattle, WA 98109 USA;

    UCL, Dept Cell & Dev Biol, London WC1E 6BT, England|UCL, Sainsbury Wellcome Ctr, London W1T 4JG, England;

    HHMI, Janelia Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA;

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