Fully integrated silicon probes for high-density recording of neural activity.
Fully integrated silicon probes for high-density recording of neural activity.
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DOI：
10.1038/nature24636
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发表时间：
2017-11-08
期刊：
影响因子：
64.8
通讯作者：
Harris TD
中科院分区：
文献类型：
--
作者：
Jun JJ;Steinmetz NA;Siegle JH;Denman DJ;Bauza M;Barbarits B;Lee AK;Anastassiou CA;Andrei A;Aydın Ç;Barbic M;Blanche TJ;Bonin V;Couto J;Dutta B;Gratiy SL;Gutnisky DA;Häusser M;Karsh B;Ledochowitsch P;Lopez CM;Mitelut C;Musa S;Okun M;Pachitariu M;Putzeys J;Rich PD;Rossant C;Sun WL;Svoboda K;Carandini M;Harris KD;Koch C;O'Keefe J;Harris TD
感觉、运动和认知操作涉及跨越大脑表层和深层结构的多个区域的大量神经元群的协调行动。现有的细胞外探针记录神经活动具有优异的空间和时间（亚毫秒）分辨率，但每柄只有几十个神经元。光学Ca2+成像提供了更多的覆盖范围，但缺乏时间分辨率来可靠地区分单个尖峰，并且不能测量局部场电位。到目前为止，没有一种与不受约束的动物兼容的技术能够将高时空分辨率与大体积覆盖相结合。为了满足这一需求，我们设计、制造并测试了一种名为Neuropixels的新型硅探针。每个探头有384个记录通道，可编程地寻址960个CMOS处理兼容的低阻抗TiN站点，这些站点具有单个10毫米长，70 × 20微米截面的柄。6x9毫米探头底座是用单芯片上的刀柄制造的。电压信号经过滤波、放大、复用和数字化处理，可直接从探头传输无噪声的数字数据。密集的记录位点和高通道数的结合，从植入小鼠和大鼠的每个探针的数百个神经元中产生了隔离良好的尖峰活动。使用两个探针，从清醒的小鼠的五个大脑结构中同时记录了700多个分离良好的单个神经元。神经像素探针的完全集成功能和小尺寸允许在自由运动的动物中记录来自多个大脑结构的大量神经元。这种高性能电极技术和可扩展芯片制造方法的结合，为记录行为过程中全脑神经活动开辟了道路。
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 Ca2+ imaging offers more coverage but lacks the temporal resolution to reliably distinguish individual spikes and does not measure local field potentials. To date, no technology compatible with unrestrained animals has combined high spatiotemporal resolution with large volume coverage. To satisfy this need, we designed, fabricated, and tested a new silicon probe called Neuropixels. Each probe has 384 recording channels that can programmably address 960 CMOS processing-compatible low-impedance TiN sites that tile a single 10 mm long, 70x20 µm cross section shank. The 6x9 mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed, and digitized on the base, allowing noise-free digital data transmission directly 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 simultaneously recorded from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed recording large populations of neurons from multiple brain structures in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens the path to record brain-wide neural activity during behavior.
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