Department of Chemistry and Chemical Biology, Center for Brain Science, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1882-7. doi: 10.1073/pnas.0914737107. Epub 2010 Jan 19.
Revealing the functional connectivity in natural neuronal networks is central to understanding circuits in the brain. Here, we show that silicon nanowire field-effect transistor (Si NWFET) arrays fabricated on transparent substrates can be reliably interfaced to acute brain slices. NWFET arrays were readily designed to record across a wide range of length scales, while the transparent device chips enabled imaging of individual cell bodies and identification of areas of healthy neurons at both upper and lower tissue surfaces. Simultaneous NWFET and patch clamp studies enabled unambiguous identification of action potential signals, with additional features detected at earlier times by the nanodevices. NWFET recording at different positions in the absence and presence of synaptic and ion-channel blockers enabled assignment of these features to presynaptic firing and postsynaptic depolarization from regions either close to somata or abundant in dendritic projections. In all cases, the NWFET signal amplitudes were from 0.3-3 mV. In contrast to conventional multielectrode array measurements, the small active surface of the NWFET devices, approximately 0.06 microm(2), provides highly localized multiplexed measurements of neuronal activities with demonstrated sub-millisecond temporal resolution and, significantly, better than 30 microm spatial resolution. In addition, multiplexed mapping with 2D NWFET arrays revealed spatially heterogeneous functional connectivity in the olfactory cortex with a resolution surpassing substantially previous electrical recording techniques. Our demonstration of simultaneous high temporal and spatial resolution recording, as well as mapping of functional connectivity, suggest that NWFETs can become a powerful platform for studying neural circuits in the brain.
揭示自然神经元网络中的功能连接对于理解大脑中的电路至关重要。在这里，我们展示了在透明衬底上制造的硅纳米线场效应晶体管（Si NWFET）阵列可以可靠地与急性脑切片接口。NWFET 阵列可以轻松设计为在广泛的长度范围内进行记录，而透明器件芯片则可以对单个细胞体进行成像，并识别上下组织表面健康神经元的区域。同时进行的 NWFET 和膜片钳研究使明确识别动作电位信号成为可能，纳米器件还可以更早地检测到其他特征。在不存在和存在突触和离子通道阻滞剂的情况下，在不同位置进行 NWFET 记录，使这些特征可以分配给靠近胞体或富含树突投射的区域的突触前发射和突触后去极化。在所有情况下，NWFET 信号幅度均为 0.3-3 mV。与传统的多电极阵列测量相比，NWFET 器件的小有效表面积（约 0.06 微米 2 ）提供了高度局部化的神经元活动复用测量，具有证明的亚毫秒时间分辨率，并且显著优于 30 微米的空间分辨率。此外，使用 2D NWFET 阵列进行的复用映射揭示了嗅觉皮层中空间异质的功能连接，其分辨率大大超过了先前的电记录技术。我们同时进行高时间和空间分辨率记录以及功能连接映射的演示表明，NWFET 可以成为研究大脑中神经电路的强大平台。
