Jun James J, Steinmetz Nicholas A, Siegle Joshua H, Denman Daniel J, Bauza Marius, Barbarits Brian, Lee Albert K, Anastassiou Costas A, Andrei Alexandru, Aydın Çağatay, Barbic Mladen, Blanche Timothy J, Bonin Vincent, Couto João, Dutta Barundeb, Gratiy Sergey L, Gutnisky Diego A, Häusser Michael, Karsh Bill, Ledochowitsch Peter, Lopez Carolina Mora, Mitelut Catalin, Musa Silke, Okun Michael, Pachitariu Marius, Putzeys Jan, Rich P Dylan, Rossant Cyrille, Sun Wei-Lung, Svoboda Karel, Carandini Matteo, Harris Kenneth D, Koch Christof, O'Keefe John, Harris Timothy D
HHMI Janelia Research Campus, 19700 Helix Drive, Ashburn, Virginia 20147, USA.
UCL Institute of Neurology, University College London, London WC1N 3BG, UK.
Nature. 2017 Nov 8;551(7679):232-236. doi: 10.1038/nature24636.
Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca imaging 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 TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 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.
感觉、运动和认知操作涉及多个脑区中浅层和深层结构的大量神经元群体的协同作用。现有的细胞外探针能够以出色的空间和时间（亚毫秒级）分辨率记录神经活动，但每条探针只能记录几十 个神经元的活动。光学钙成像能够覆盖更多神经元，但缺乏可靠区分单个动作电位所需的时间分辨率，并且无法测量局部场电位。到目前为止，还没有一种适用于无束缚动物的技术能够将高时空分辨率与大面积覆盖相结合。在这里，我们设计、制造并测试了一种名为Neuropixels的新型硅探针，以满足这一需求。每条探针有384个记录通道，可对960个与互补金属氧化物半导体（CMOS）处理兼容的低阻抗氮化钛（TiN）位点进行可编程寻址，这些位点覆盖在单个10毫米长、70×20微米横截面的探针杆上。6×9毫米的探针基座与探针杆在同一芯片上制造。电压信号在基座上进行滤波、放大、多路复用和数字化，从而实现从探针直接传输无噪声数字数据。密集的记录位点和高通道数相结合，使得植入小鼠和大鼠体内的每条探针都能从数百个神经元中记录到分离良好的动作电位活动。使用两条探针，在一只清醒小鼠的五个脑结构中同时记录到了700多个分离良好的单个神经元。Neuropixels探针的全集成功能和小尺寸使得在自由活动的动物中能够记录来自多个脑结构的大量神经元活动。这种高性能电极技术与可扩展芯片制造方法的结合为在行为过程中记录全脑神经活动开辟了一条道路。
